### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY



### Date:

Subject: WASHINGTON, D.C. 20460



### February 28, 20 13 OFFICE OF CHEMICA L SAFETY

AND POLLUTION PREVENTION



### Cyantraniliprole. Occupational and Residential Exposure and Risk Assessment

for the Proposed New Uses of the New Active Insecticide, including Agricultural

Uses on Brassica 

### (Cole) Leafy Vegetables (Group 5)

, Bulb Vegetables (G r oup 3- 07), Bushberries (Group 13 -07B)

, C itru s Fruit (Group I 0-10), Cotton, Cucurbit Vegetables (Group 9), Fruiting Vegetables (Group 8-10), Leafy Vegetables (nonBrassica) 

### (Group 4), Oilseeds (G roup 20)

, Pome Fruits (Group 11-1 0), Stone

Fruits (Group 12)

, Tree Nuts (Group 14), Tuberous and Corm Vegetables (Subgroup 1 C); Seed Trea tment Uses on Canola, Mustard Seed, Sunflowers, and
Potatoes; and Residential, Commercial

, and Agricultural Uses on Ornamentals, Turfgrass (including Sod Farms), and Structural Buildings (including Indo or Crack/Crevice and Outdoor Broadcast).

PC Code: 090098 DP Barcod e: 0407964

Decision No.: 451670 Registration Nos.: 352 -IAE

, 352-IAG

, 352-IAI

, 352-IAL

, 253-IAN

, 352-

ILA

, 352- ILI

, 352 -ILO

, 352-ILT, 100-RUEE

, 100-RUEG

, 100 -R UEN

, 100-RUER, 100-RUEU, 100-RURI

Petition No.: I F7894

Risk Assessment Type: OccupationaVResidential Exposure A ssessme nt

TXR No.: NA

MRID No.: NA



### From: Nancy J. 

### Tsaur, Chemist

Risk Assessment Branch 3 (RAB

Health Effec ts Division (7509P) Regulatory Action: Section 3

Case No

. : NA

CAS No.: 736994 -6 3

- 1

40 CFR: to be determined



### Through: Barry O'Keefe, Senior Biologist, ORE Team Leader



# . B. 0

# ~ Risk Assessment Branch 3 (RAB3)

Health Effects Division (7509P)

and 

# ttL

Wade Britton

, Biologist 

### 'M/,( 

### I 

# 11

Matthew C r owley, Senior 

## Bt agist, E:::I!i Co-Chair Exposure Science Advisory Committee (ExpoSAC)

Health Effects Division (7509P)

To: Thomas Harris / John Hebert

, RM #0 7


## Insecticide Rodenticide Branch (IRB)

Division (7505P)

Page 1 of 47

### Introduction

t

· - · 

### The Registration Division (RD) requested that the Health Effects Division (HED) conduct an occupationa l and residential exposure and r i sk assessment fo r a ll o f the proposed new uses of the

new active insecticide

, cyantraniliprole, including agricultural uses on 

### Brassica (Cole) leafy vegetables (Group 5), bulb vegetab l es (Group 3-07), bushberries (Group 13-07B), citrus fruits (Group 1 0

- 10), cotton, cucurbit vegetables (Group 9), fruiting vegetables (Group 8-1 0)

, leafy vegetab l es 

### (non-Brassica) (Group 4)

, oilseeds (Group 20), pome fruits (Group 11-10), potatoes,

stone fruits (Group 12), sunflowers, tree nuts (Group 14), tu berous and corm vegetables (Subgroup I C); seed treatment uses on canola, mustard seed, sunflowers, and potatoes; and residential, commercial, and agricultural uses on ornamentals, turfgrass (including sod farms),

and structural buildings (including indoor crack/crevice and outdoor broadcast).



### It is HED policy to use the best available data to assess exposure. Severa l sources of generic

data were used in t his assessment as surrogate data in th e absence of chemical

- specific data, including Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1 ); the Agricultura l Handler Exposure Task Force (AHETF) database; the Outdoor Residential Exposure T ask Force

' (ORETF) database; ExpoSAC Policy 14 (SOPs for Seed Treatment); the Residential SOPs (Lawns/Turf; Gardens and Trees; In door Environmen ts ). Some ofthese data are proprietary, and subject to the data protection provisions of the Federal Insec t icide, Fungicide

, and Rodent i cide

Act (FIFRA).

Note: This memorandum was reviewed by the Exposure Science Advisory Committee (ExpoSAC) on January 17, 2013

.

: i :



### Page 2 of 47

### Page 3 of 47 Table of Contents

1.0 Executive Summary

................................ ................................ ................................ ............. 4

2.0 Risk Assessment Conclusions and Recommendations

................................ ........................ 6

2.1 Summary of Risk Estimates

................................ ................................ ............................. 6

2.2 Label Recommendations from Occupational Assessment

................................ ............... 6

2.3 Label Recommendations from Residential Assessment

................................ .................. 7

2.4 Data Deficiencies and Requirements

................................ ................................ ............... 7

3.0 Hazard Characterization

................................ ................................ ................................ ....... 7

4.0 Use Profile

................................ ................................ ................................ ......................... 11

5.0 Residential Exposure and Risk Estimates

................................ ................................ .......... 19

5.1 Residential Handler Exposure/Risk Estimates

................................ ............................... 19

5.2 Residential Post

- Application Exposure/Risk Estimates

................................ ................. 22

5.3 Residential Risk Estimates for Use in Aggregate Assessment

................................ ...... 25

5.4 Spray Drift

................................ ................................ ................................ ...................... 26

5.5 Residential Bystander Post

- Application Inhalation Exposure

................................ ....... 26

6.0 Occupational Exposure and Risk Estimates

................................ ................................ ...... 27

6.1 Agricultural Occupational Handler Expo sure/Risk Estimates

................................ ....... 27

6.2 Seed Treatment Occupational Handler Exposure/Risk Estimates

................................ . 34

6.3 Occupational Post

- Application Exposure/Risk Estimates

................................ ............. 38

6.4 Restricted Entry Interval

................................ ................................ ................................ 39 Appendix A. Summary of Occupational Handler Non

- Cancer Algorithms

................................ 41 Appendix B. Summary of Residential Post

- Application Non

- Cancer Algorithms

..................... 42 Appendix C. Human Equivalent Concentrations and Human Equivalent Dose Calculations

. 45

### Page 4 of 47

1.0 Executive Summary

Cyantraniliprole is a new second

- generation ryanodine receptor (RyR) insecticide currently undergoing global joint review. It has been jointly developed by DuPont and Syngenta, with a proposal (PP# 1F7894 ) for one technical product and 14 U.S. end

- use product (EP) registrations, including agricultural food

- uses.

Cyantraniliprole is a systemic insecticide belonging to the diamide class of chemistry, mobile in

both the xylem and phloem. The mode of action is through its binding with insect RyR s. This causes muscle contraction, which leads to paralysis and eventual death of t he insect.

Proposed Use Profile The agricultural uses include foliar, soil, and seed treatment to various crops including cotton, fruits, oilseeds, and vegetables. The residential use sites include turfgrass, ornamentals, and structural buildings (including indoor crack/crevice and outdoor broadcast).

Exposure Profile

Non

- occupational an d occupational e xposures to cyantraniliprole a re expected for short

- and

intermediate

- term durations. The dermal route of exposure is not assessed because there is no dermal hazard. The proposed residential u se s (turf, ornamentals, and indoor crack/crevi ce) result

in inhalation exposures for adults (handlers) and post

- application incidental oral exposures for children (1 to <2 years old)

.

Hazard Characterization

The toxicity data indicate that cyantraniliprole produce s liver effects at lower dose levels

. Do gs appear to be more sensitive than rats and mice. A de rmal point of departure (POD) i s not cho sen because systemic toxicity i s not seen in 28

- day dermal toxicity in rats at the limit dose (1

, 000 mg/kg/day). The short

- and intermediate

- term inhalatio n POD s are based on the results of a 28

- day inhalation toxicity study in rats. To determine the inhalation PODs for residential and occupational exposure, the Agency’s Reference Concentration (RfC) methodology i s used to

calculate human equivalent concentration s (HEC s ). The HEC s a re then converted to respect ive human equivalent doses : NOAEL = 7

. 2 mg/kg/day for residential exposure and NOAEL = 10.08 mg/k g/day for occupational exposure . The short

- and intermediate

- term incidental oral POD is

based o n two co

- critical studies: the 28

- day and 90

- day oral toxicity studies in dogs (NOAEL = 3.0 mg/kg/day)

. Cyantraniliprole is not acutely toxic; it is classified as Toxicity Category IV for all routes of exposure (dermal, oral, and inhalation). There are n o genotoxicity, mutagenicity, neurotoxicity, or immunotoxicity concerns. Nor are there developmental or reproductive toxicity

concerns. Cyantraniliprole is classified as “ Not L ikely to be Carcinogenic to Humans” based on

the absence of increased tumor in cidence in acceptable/guideline carcinogenicity studies in rats

and mice.

Combining Exposures/Risk Estimates The dermal route of exposure does not need to be combined with another route of exposure or included in the aggregate risk assessment because there is no dermal hazard

.

### Page 5 of 47

Summary of Residential Handler Non

- Cancer Exposure and Risk Estimates

Handler risk estimates for all scenarios are not of concern. Short

- term inhalation MOEs range

from 2 2

, 0 00 to 22 0 ,000,000.

Summary of Residential Post

- Application Non

- Cancer Exposure and Risk Estimates Although residential dermal exposure is expected following the treatment of turf or cracks/crevices , a quantitative post

- application dermal risk assessment was not conducted because a dermal hazard was not identified for cyantraniliprole. S hort

- term incidental oral p ost

application risk estimates (which are protective of intermediate

- term risk estimates) for all

scenarios are not of concern to HED ( MOEs range from 290 to 1,000 ,000)

.

Summary of Aggregate The most protective risk estimate for adult handler inhalation exposures is based on dry flowable application to ornamentals which results in an MOE of 2 2

, 0 00. The most protective risk

estimate for children’s post

- application incidental oral exposures is based on indoor liquid crack/crevice application to carpets which results in an MOE of 290.

Summary of Occupational Handler Non

- Cancer Exposure and Risk Estimates The results of the occupational handler expos ure and risk assessment indicate that short

- and

intermediate

- term inhalation risks are not of concern at baseline mitigation without personal protective equipment ( PPE)

. S hort

- and intermediate

- term MOE s rang e from 1,200 to 3,9 00,000

. Note that o nly engineering control (enclosed cockpit) data are available to assess

risks to handlers operating aircrafts. Seed treatment MOEs range from 370 to 4,000 for primary handlers (treaters) and 2,200 to 190,000 for secondary handlers (planters).

Summary of Occu pational Post

- Application Non

- Cancer Exposure and Risk Estimates An occupational post

- application dermal exposure and risk assessment was not conducted because a dermal hazard was not identified for cyantraniliprole. Based on the Agency's current practice s, a quantitative non

- cancer occupational post

- application inhalation exposure assessment was not performed for cyantraniliprole at this time. If new policies or procedures are put into place, the Agency may revisit the need for a quantitative occupationa l post

- application inhalation exposure assessment for cyantraniliprole.

Restricted Entry Interval

The technical form of c yantraniliprole meets the criteria for a 4

- hour REI. However, t wo of the proposed EPs (EPA Reg. No. 352

- ILT and EPA Reg. No. 352

- ILI) have been identified as dermal sensitizers, so a 12

- hour REI is required to protect agricultural workers from post

application exposures to cyantraniliprole. Aside from these two products, a 4

- hour REI is adequate to protect agricultural workers from pos t

- application exposures to cyantraniliprole

.

Human Studies Review This risk assessment relies in part on data from studies in which adult human subjects were intentionally exposed to a pesticide or other chemical. These data, which include Pesticide Handlers Exposure Database Version 1.1 (PHED 1.1); the Agricultural Handler Exposure Task Force (AHETF) database; the Outdoor Residential Exposure Task Force (ORETF) database ; ExpoSAC Policy 14 and 15.1 (SOPs for Seed Treatment); the Residential SOPs ( Lawns/Turf;

### Page 6 of 47

Gardens and Trees; Indoor Environments ), are (1) subject to ethics review pursuant to 40 CFR 26, (2) have received that review, and (3) are compliant with applicable ethics requirements. For certain studies, the ethics review may have i ncluded review by the Human Studies Review Board. Descriptions of data sources, as well as guidance on their use, can be found at the Agency website 1



### .

2.0 Risk Assessment Conclusions and Recommendations

There are no occupational/residential risk estim ates of concern associated with the proposed new

uses of cyantraniliprole

.

2.1 Summary of Risk Estimates

Occupational Exposure and Risk Estimates The results of the occupational handler exposure and risk assessment indicate that short

- and

intermediate

- term inhalation risks do not exceed HED’s level of concern (i.e. the LOC is an MOE < 3 0 for short

- term exposures and an MOE < 100 for intermediate

- term exposures ) at baseline mitigation (no PPE)

. Since the short

- and intermediate

- term PODs are the same, the

inhalation MOE s are also the same, ranging from 1,200 to 3, 9 00,000

. Dermal handler and post

application exposure and risk assessme nt s w ere not conducted because a dermal hazard was not identified for cyantraniliprole.

Residential Exposure and Risk Estimates The results of the residential handler exposure and risk assessment indicate that short

- term
inhalation risks do not exceed HED ’s LOC (i.e. an MOE < 30). Handler risk estimates for all

scenarios are not of concern. Short

- term inhalation MOEs range from 2 2, 0 00 to 22 0 ,000,000. Although residential dermal exposure is expected following the treatment of turf or cracks/crevices, a qu antitative post

- application dermal risk assessment was not conducted because a dermal hazard was not identified for cyantraniliprole. Short

- term incidental oral p ost

application risk estimates for all scenarios are not of concern to HED ( MOEs range from 290 to 1,000 ,000) because they exceed the LOC for incidental oral exposure (i.e. an MOE < 100)

. Furthermore, short

- term incidental oral post

- application risk estimates are protective of

intermediate

- term because the POD is the same.

2.2 Label Recommenda tions from Occupational Assessment

The labeled use pattern for EPA Reg. No. 352

- IAG must be clarified. The proposed label states both: “For vegetable transplants in and around greenhouses,” as well as “Do not apply to greenhouse or field grown vegetable s, only apply to vegetable transplants grown in enclosed structures.” Note that both use patterns have been considered in this risk assessment and neither would result in occupational risk estimates of concern.

1 http://www.epa.gov/pesticides/science/handler

- exposure

- data.html and http://www.epa.gov/pesticides/science/post

- app

- exposure

- data.html

### Page 7 of 47

2.3 Label Recommendations from Residential Assessment

There are no label recommendations based on the residential assessment.

2.4 Data Deficiencies and Requirements

There are no data deficiencies or data requirements for the new active ingredient, cyantraniliprole.

3 .0 Hazard Characterization

Cyantraniliprole belong s to the anthranilic diamide class of pesticides. Anthranilic diamide s control insects through unregulated activation of RyR channels leading to internal calcium store depletion that impairs regulation of muscle contraction. Insects exposed to a nthranilic diamide s exhibit general lethargy and muscle paralysis ultimately followed by death

.

The risk assessment for cyantraniliprole is based on a well

- characterized and complete toxicology database. While unregulated activation of RyR channels lead s to insect death, the insect RyR are shown to be 350 to >2500 times more sensitive than those of mammals. In general, cy antraniliprole administration produces both adverse and adaptive changes in the liver, thyroid gland, and adrenal cortex. With repeated dosing, consistent finding s of mild to moderate increases in liver weights across multiple species (rats, mice, dogs) a re observed

. Dogs appear to be more sensitive than rats and mice; cyantraniliprole produces adverse liver effects (increases in alkaline phosphatase, decreases in cholesterol, and decreases in albumin) in dogs at lower dose

levels than in rats. In additi on, the liver effects in the dog show progressive severity with increased duration of exposure. The available data also show thyroid hormone homeostasis i s altered in rats following exposure to cyantraniliprole after 28 or 90 days. However, cyantranilipr ole is not a direct thyroid toxicant.

A de rmal point of departure (POD) i s not cho sen because systemic toxicity i s not seen in 28

- day dermal toxicity in rats at the limit dose (1

, 000 mg/kg/day). The short

- and intermediate

- term
incidental oral POD is bas ed on two co

- critical studies: the 28

- day and 90

- day oral toxicity studies in dogs (NOAEL = 3.0 mg/kg/day). The short

- and intermediate

- term inhalation POD s

are based on the results of a 28

- day inhalation toxicity study in rats (NOAEL = 10.08 mg/kg/day for occupational exposure, NOAEL = 7.2 mg/kg/day for residential exposure).

To determine the inhalation PODs for residential and occupational exposure, the Agen cy’s Reference Concentration (RfC) methodology was used to calculate human equivalent concentrations (HECs). These calculations are detailed in Appendix B, Section B.4. The HECs

are based on a 28

- day rat inhalation study which show no systemic or port of entry effects at the highest concentration (NOAEL = 0.1 mg/L). Because the 28

- day study was conducted 6 hours per day, 5 days per week, the HECs are adjusted to represent both residential and occupational exposure scenarios. For residential exposure, th e HEC is adjusted to represent continual exposure for 24 hours per day, 7 days per week. For occupational exposure, the HEC was adjusted to represent an average work week for 8 hours per day, 5 days per week. The short

term inhalation HEC of 0.21 mg/L ca lculated for residential exposures is then converted to a

### Page 8 of 47

human equivalent dose NOAEL of 7.2 mg/kg/day to allow for comparison to estimated residential inhalation doses (which are in units mg/kg/day). The short

- and intermediate

- term
inhalation HEC of 0.0 5 mg/L calculated for occupational exposures was also converted to a human equivalent dose NOAEL of 10.08 mg/kg/day to allow for comparison to estimated occupational inhalation doses (which are in units mg/kg/day).

Although a route specific 28

- day inhalat ion study is use d to establish the intermediate

- term POD,

s ome of the t oxicity data indicate a progression in toxicity with time. The data indicate an approximate three

- fold difference in the LOAEL between a 28

- day oral toxicity stud y in rats (53 mg/kg/da y) and a reproduction study in rats (14 mg/kg/day). Theref ore, an uncertainty factor of

3X i s selected to account for using a POD from a short

- term 28

- day day inhalation study to

assess intermediate

- term exposure (1

- 6 months)

. Given that the 28

- day inha lation study does not show any adverse effects at the highest concentration, HED acknowledges that the application of 3X is a conservative approach. However, given the progression of liver effects seen in oral studies, HED cannot rule out the potential fo r adverse port of entry or systemic effects given longer exposures.

In accordance with the requirements of the FQPA (1996), HED has considered the potential for

concurrent cyantraniliprole exposure via oral, dermal, and inhalation routes. HED aggregates exposure from different routes for each population if the same toxic effects are seen for that duration of exposure by each route. The dermal route of exposure does not need to be combined with another route of exposure or included in the aggregate risk a ssessment because there is no

identified dermal hazard. There are no genotoxicity, mutagenicity, neurotoxicity, or immunotoxicity concerns. Nor are there developmental or reproductive toxicity concerns. Cyantraniliprole is classified as “ Not L ikely to be Carcinogenic to Humans” based on the absence of increased tumor incidence in acceptable/guideline carcinogenicity studies in rats and

mice.

Acute Toxicity

Table 3.1. Summary of Acute Toxicity Data for Cy antraniliprole (Technical Active Ingredient )

Type of study MRID Results Toxicity Category

Acute oral LD 50 — m ouse 48119957 LD 50 >5000 mg/kg IV

Acute oral LD 50 —

rat 48119952 LD 50 >5000 mg/kg IV

Acute dermal LD 50 —

rat 48119953 LD 50 >5000 mg/kg IV

Acute inhalation LC 50 (4 h r )

— rat 48119958 LC 50 > 5.2 mg/L IV

Skin irritation

—

rabbit 48119954 Not irritating

NA Eye irritation

—

rabbit 48119955 Slightly irritating; clearing by 72

hours Eye irritation

—

rabbit 48208421 Not irritating

Skin sensitisation

— mouse (local lymph node assay) 48208422 Not sensiti z ing

Skin sensitisation

— mouse (local lymph node assay) 48208423 Not sensitizing

Skin sensitisation

— guinea pig (Maximisation test) 48119984 Not Sensiti z ing

### Page 9 of 47

Toxicological PODs Used for Risk Assessment

Table 3. 2 . Summary of Toxicological Do ses and Endpoints for C yantraniliprole for Use in Non

Occupational /Residential Human Health Risk Assessments a

Exposure/

Scenario Point of

Departure Uncertainty/

FQPA Safety

Factors RfD, PAD,

Level of

Concern for

Risk

Assessment Study and Toxicological Effects

Acute Dietary (General Population, including

Infants and

Children

and

Females 13

- 49 years of age) An effect attributed to a single dose was not identified in the toxicology database



### .

Incidental

Oral

Short

- T erm (1

- 30 days)

and

I ntermediate

- T erms (1

- 6 months) NOAEL =

3 mg/kg/day UF A = 10X

UF H = 10X FQPA SF =

1X LOC = 100 28

- day and 90

- day oral study in dogs.

28

- day LOAEL = 35 mg/kg/day (lowest dose tested) based on decreases in body weight, food consumption, food efficiency, and changes in clinical chemistry (↑ALP, ↓ cholesterol and ↓ albumin).

90

- day LOAEL = 32 mg/kg/day based on a

collection of treatment

- related effects indicative of liver toxicity. The effects included decreases in total protein, albumin, and cholesterol in mal es and females; increases in alkaline p hosphatase in males and females; increases in alan ine aminotransferase in females; and increase s in liver weights in males

and females.

Dermal

Short

- Term (1

- 30 days) A toxicity endpoint was not identified

.

S ystemic toxicity was not seen in 28

- day dermal toxicity in rats at the limit dose (1000 mg/kg/day) . T here are no concerns for developmental or reproductive toxicity or neurotoxicity.

Inhalation

Short

- Term (1

- 30 days) NOAEL =

0.1 mg/L UF A = 3 X b

UF H = 10 X FQPA SF = 1 X LOC = 30 28

- day in halation toxicity study in rats

. A LOAEL was not established because the highest

concentration tested (0.1 mg/L) did not demonstrate any adverse portal of entry or systemic effects. HEC = 0005 mg/L

HED = 7.2 mg/kg/day Cancer (oral, dermal, inhalation) Classification: “Not likely to be Carcinogenic to Humans” based on data showing lack of

trea tment

- related increase in tumor incidence in the rat and mouse carcinogenicity studies.

M utagenic concern was not reported in the mutagenicity studies.

a Point of Departure (POD) = A data point or an estimated point that is derived from observed dose

- response data and used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in sensitivit y among members of the human population (intraspecies). FQPA SF = FQPA Safety Factor. LOC = level of concern. HED = human equivalent dose. HEC = human equivalent concentration.

b T he magnitude of the UFs applied is dependent on the methodology used to c alculate risk. The RfC methodology takes into consideration the pharmacokinetic (PK) differences, but not the pharmacodynamic (PD) differences . Consequently, the UF for interspecies extrapolation may be reduced to 3X (to account for the PD differences).

### Page 10 of 47

Table 3. 3 . Summary of Toxicological Do ses and Endpoints for C yantraniliprole for Use in Occupational

Human Health Risk Assessments a

Exposure/

Scenario Point of

Departure Uncertainty/

FQPA Safety

Factors RfD, PAD,

Level of

Concern for

Risk

Assessment Study and Toxicological Effects

Dermal

Short

- Term (1

- 30 days)

and

I ntermediate

- T erms (1

- 6 months) A toxicity endpoint was not identified

.

S ystemic toxicity was not seen in 28

- day dermal toxicity in rats at the limit dose (1000 mg/kg/day) . T here are no concerns for developmental or reproductive toxicity or neurotoxicity.

Inhalation

Short

- Term (1

- 30 days) NOAEL =

0.1 mg/L

UF A = 3X b

UF H = 10X LOC = 30 28

- day inhalation toxicity study in rats

. A LOAEL was not established because the highest

concentration tested (0.1 mg/L) did not demonstrate any adverse portal of entry or systemic effects. HEC =

0. 05 mg/L

HED = 10.08 mg/kg/day

Inhalation

Intermediate

- Term (1

- 6 months) NOAEL =

0.1 mg/L

UF A = 3X

UF H = 10X

UF DB = 3X c LOC = 100 28

- day in halation toxicity study in rats.

A LOAEL was not established because the highest

concentration tested (0.1 mg/L) did not demonstrate any adverse portal of entry or systemic effects. HEC =

0

. 05 mg/L

HED =

10.08 mg/kg/day Cancer (oral, dermal, inhalation) Classification: “Not likely to be Carcinogenic to Humans” based on data showing lack of

trea tment

- related increase in tumor incidence in the rat and mouse carcinogenicity studies.

M utagenic concern was not reported in the mutagenicity studies.

a Point of Departure (POD) = A data point or an estimated point that is derived from observed dose

- response data and used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures.

NOAEL = no ob served adverse effect level. LOAEL = lowest observed adverse effect level. HED = human equivalent dose.

HEC = human equivalent concentration. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies).

UF H = potential variation i n sensitivity among members of the human population (intraspecies). UF DB = database uncertainty

factor: use of a short

- term study for intermediate

- term risk assessment. FQPA SF = FQPA Safety F actor. LOC = level of

concern. b T he magnitude of the UFs appli ed is dependent on the methodology used to calculate risk. The RfC methodology takes into consideration the pharmacokinetic (PK) differences, but not the pharmacodynamic (PD) differences . Consequently, the UF for interspecies extrapolation may be reduced to 3X (to account for the PD differences).

c A route specific 28

- day inhalation study is used to establish the intermediate term exposure toxicity endpoint and point of departure. Some of the toxicity da ta on cyantraniliprole indicate that there was a pro gression in toxicity with time. The data

indicate a ~three

- fold difference in the LOAEL between a 28

- day oral toxicity stud y in rats (53 mg/kg/day) and a reproduction study in rats (14 mg/kg/day) . Therefore, an uncertainty factor of 3X was selected to account for using a POD from a short

- term
28

- day day inhalation study to assess intermediate

- term exposure (1

- 6 months).



### Absorption A dermal absorption factor i s not used in this assessment because a dermal toxicity POD i s not
identified based on a 28

- da y dermal toxicity study in rats

. Since the short

- and intermediate

- term
inhalation PODs a re based on a route

- specific toxicity stud y
, absorption factors a re not necessary to estimate inhalation exposure.

### Page 11 of 47

Body Weight The standard body weight for the gener al population (80 kg) i s used for all adult exposure scenarios covered in this risk assessment since the endpoints selected a re not developmental

and/or fetal effects. The standard body weight for children 1 to <2 years old is 11 kg.

4 .0 Use Profile

Table 4.1

. Summary of Proposed Directions for Use of Cyantraniliprole (DuPont and Syngenta Labels)

Application Timing, Type, and Equipment Formulation

[EPA Reg. No.]

Trade Name a Maximum

Application

Rate Max. No.

of Apps per

Season Max.

Seasonal Application

Rate RTI Use Directions and Limitations

days

Brassica (Cole) Leafy Vegetables (Group 5)

Soil at Planting (in

- furrow spray, transplant water treatment, hill drench, surface band, soil shank injection) 18.66% SC

[352

- IAN]
VerimarkTM 0.176

lb ai/A

0.00202 lb ai/gal 1 0.176

lb ai/A N/A Only to be applied to the soil by ground or drip

chemigation application equipment. Must be applied uniformly in the root zone. Do not make aerial or airblast applications

. Do not treat plants being grown for transplanting in nurseries. Use this product only in commercial and farm plantings. May be used on crops grown for seed production.

Foliar (ground, aerial) 10.20% SE

[352

- ILO]
ExirelTM 0.133

lb ai/A

0.00443 lb ai/gal N/S

0.4

lb ai/A 5 Do not treat plants grown for transplanting. Do

not apply to the soil or through drip irrigation systems. Use this product only in commercial and farm plantings. May be used on crops grown for seed production. Adjuvants may be used (methylated s eed oils; petroleum oil

concentrates ; non

- ionics; organosilicones/ organosilicates). Use a minimum of 10 gallons per acre for all vegetable crops.

Soil ( i n

- furrow spray at seeding or transplanting; post seeding, post transplant, hill drench; drip (trickle) chemigation;

shanked into root zone) 20.0% WG

[100

- RUER]

A16901B CP 0.175

lb ai/A

0.0175 lb ai/gal 1 NA Use this product only in commercial and farm plantings. Do not use in greenhouses. Do not treat plants grown for transplanting. Apply within 21 days of planting or transplanting. Make only one soil application per growing

season.

Foliar (ground, aerial, chemigation) 20.0% WG

[100

- RUER]

A16901B CP 0.0875

lb ai/A

0.00875 lb ai/gal N/S 7 Use this product only in commercial and farm plantings. Do not use in greenhouses. Do not treat plants grown for transplanting. Apply within 21 days of planting or transplanting. Use

a m inimum of 10 gal water per acre for ground application

. Bulb Vegetables (Group 3

- 07)

Foliar (ground, aerial) 10.20% SE

[352

- ILO]
ExirelTM 0.133

lb ai/A

0.00443 lb ai/gal N/S 0.4

lb ai/A 5 Do not treat plants grown for transplanting. Do

not apply to the soil or through drip irrigation systems. Use this product only in commercial and farm plantings. May be used on crops grown for seed production. Adjuvants may be used (methylated seed oil s; petroleum oil

con centrates; non

- ionics; organosilicones/ organosilicates). Use a minimum of 10 gallons per acre for all vegetable crops.

### Page 12 of 47

Table 4.1

. Summary of Proposed Directions for Use of Cyantraniliprole (DuPont and Syngenta Labels)

Application Timing, Type, and Equipment Formulation

[EPA Reg. No.]

Trade Name a Maximum

Application

Rate Max. No.

of Apps per

Season Max.

Seasonal Application

Rate RTI Use Directions and Limitations

days

Foliar (ground, aerial

, chemigation ) 10.26% OD

[352

- ILT]
BeneviaTM 0.133

lb ai/A

0.0133 lb ai/gal N/S 0.4

lb ai/A 5 Do not treat plants grown for transplanting. Do

not apply to the soil or through drip irrigation systems. Use this product only in commercial and farm plantings. May be used on crops grown for seed production. Adjuvants may be used (methylated seed o ils; petroleum oil

concentrates; non

- ionics; organosilicones/ organosilicates). Use a minimum of 10 gallons per acre for bulb vegetables.

Bushberries (Group 13

- 07B)

Foliar (ground, aerial) 10.20% SE

[352

- ILO]
ExirelTM 0.133

lb ai/A

0.00443 lb ai/gal N/S 0.4

lb ai/A 5 Do not treat plants grown for transplanting. Do

not apply to the soil or through drip irrigation systems. Use this product only in commercial and farm plantings. May be used on crops grown for seed production. Adjuvants may be used (m ethylated seed oi ls; petroleum oil

concentrates; non

- ionics; organosilicones/ organosilicates). Use a minimum of 30 gallons per acre for all fruit and nut crops.

Citrus Fruits (Group 10

- 10)

Soil drench or microsprinkler chemigation 18.66% SC

[352

- IAN]
VerimarkTM 0.391

lb ai/A

0.00449 lb ai/gal 1 0.4

lb ai/A N/A For use on citrus nursery stock (trees less than 4

years old). Only to be applied to the soil by ground or drip chemigation application equipment. Must be applied uniformly in the

root zone. Do not make aerial or airblast applications

. Do not treat plants being grown for transplanting in nurseries. Use this product only in commercial and farm plantings. May be used on crops grown for seed production.

Foliar (ground, aerial) 10.20% SE

[352

- ILO]
ExirelTM 0.133

lb ai/A

0.00443 lb ai/gal N/S 0.4

lb ai/A 7 Do not treat plants grown for transplanting. Do

not apply to the soil or through drip irrigation systems. Use this product only in commercial and farm plantings. May be used on crops

g rown for seed production. Adjuvants may be used (methylated seed o ils; petroleum oil

concentrates; non

- ionics; organosilicones/ organosilicates). Use a minimum of 30 gallons per acre for all fruit and nut crops.

Cotton

Foliar (ground, aerial) 10.26% OD

[352

- ILT]
BeneviaTM 0.133

lb ai/A

0.0133 lb ai/gal N/S 0.4

lb ai/A 7 Do not treat plants grown for transplanting. Do

not apply to the soil or through drip irrigation systems. Use this product only in commercial and farm plantings. May be used on crops grown for seed production. Adjuvants may be used (methylated seed oil s; petroleum oil

concentrates ; non

- ionics; organosilicones/ organosilicates). Use a minimum of 10 gallons per acre for cotton.

### Page 13 of 47

Table 4.1. Summary of Proposed Directions for Use of Cyantraniliprole (DuPont and Syngenta Labels)

Application Timing, Type, and Equipment Formulation

[EPA Reg. No.]

Trade Name a Maximum

Application

Rate Max. No.

of Apps per

Season Max.

Seasonal Application

Rate RTI Use Directions and Limitations

Cucurbit Vegetables (Group 9)

Soil at Planting (in

- furrow spray, transplant water treatment, hill drench, surface band, soil shank injection) 18.66% SC

[352

- IAN]
VerimarkTM 0.176

lb ai/A

0.00202 lb ai/gal 1 0.176

lb ai/A N/A Only to be applied to the soil by ground or drip

chemigation application equipment. Must be applied uniformly in the root zone. Do not make aerial or airblast applications

. Do not treat plants being grown for transplanting in nurseries. Use this product only in commercial and farm plantings. May be used on crops grown for seed production. Drip chemigation 18.66% SC

[352

- IAN]
VerimarkTM 0.130

lb ai/A

0.00149 lb ai/gal 2

(1 if at

plant app is made) 0.26 0

lb ai/A 10

Foliar (ground, aerial) 10.20% SE

[352

- ILO]
ExirelTM 0.133

lb ai/A

0.00443 lb ai/gal N/S 0.4

lb ai/A 1 Do not treat plants grown for transplanting. Do

not apply to the soil or through drip irrigation systems. Use this product only in commercial and farm plantings. May be used on crops grown for seed production. Adjuvants may be used (methylated seed oil s; petroleum oil

concentrates; non

- ionics; organosilicones/ organosilicates). Use a minimum of 10 gallons per acre for all vegetable crops.

Soil (i n

- furrow spray at seeding or transplanting; post seeding, post transplant, hill drench; drip (trickle) chemigation;

shanked into root zone) 20.0% WG

[100

- RUER]

A16901B CP 0.175

lb ai/A

0.0175 lb ai/gal 1 0.4

lb ai/A NA Use this product only in commercial and farm

plantings. Do not use in greenhouses. Do not treat plants grown for transplanting. Apply within 21 days of planting or transplanting. Make only one soil application per growing

season.

Foliar (ground, aerial, chemigation) 20.0% WG

[100

- RUER]

A16901B CP 0.0875

lb ai/A

0.00875 lb ai/gal N/S 0.4

lb ai/A 7 Use this product only in commercial and farm

plantings. Do not use in greenhouses. Do not treat plants grown for transplanting. Apply within 21 days of planting or transplanting.

Use a m inimum of 10 gal water per acre for ground application

.

Fruiting Vegetables (Group 8

- 10)

Soil at Planting (in

furrow spray, transplant water treatment, hill drench, surface band, soil shank injection) 18.66% SC

[352

- IAN]
VerimarkTM 0.176

lb ai/A

0.00202 lb ai/gal 1 0.176

lb ai/A N/A Only to be applied to the soil by ground or drip

chemigation application equipment. Must be applied uniformly in the root zone. Do not make aerial or airblast applications

. Do not treat plants being grown for transplanting in nurseries. Use this product only in commercial and farm plantings. May be used on crops grown for seed production. Drip chemigation 18.66% SC

[352

- IAN]
VerimarkTM 0.130

lb ai/A

0.00149 lb ai/gal 2

(1 if at

plant app is made) 0.26 0

lb ai/A 10

### Page 14 of 47

Table 4.1. Summary of Proposed Directions for Use of Cyantraniliprole (DuPont and Syngenta Labels)

Application Timing, Type, and Equipment Formulation

[EPA Reg. No.]

Trade Name a Maximum

Application

Rate Max. No.

of Apps per

Season Max.

Seasonal Application

Rate RTI Use Directions and Limitations

Foliar (ground, aerial)

Foliar (greenhouse) 10.20% SE

[352

- ILO]
ExirelTM 0.133

lb ai/A

0.00443 lb ai/gal N/S 0.4

lb ai/A 1 Do not treat plants grown for transplanting. Do

not apply to the soil or through drip irrigation systems. Use this product only in commercial and farm plantings. May be used on crops grown for seed production. Adjuvants may be used (methylated seed oil s; petroleum oil

concentrates: non

- ionics; organosilicones/ organosilicates). Use a minimum of 10 gallons per acre for all vegetable crops.

Soil (i n

- furrow spray at seeding or transplanting; post seeding, post transplant, hill drench; drip (trickle)

chem igation;

shanked into root zone) 20.0% WG

[100

- RUER]

A16901B CP 0.175

lb ai/A

0.0175 lb ai/gal 1 0.4

lb ai/A NA Use this product only in commercial and farm

plantings. Do not use in greenhouses. Do not treat plants grown for transplanting. Apply

within 21 days of planting or transplanting. Make only one soil application per growing

season.

Foliar (ground, aerial, chemigation) 20.0% WG

[100

- RUER]

A16901B CP 0.0875

lb ai/A

0.00875 lb ai/gal N/S 0.4

lb ai/A 7 Use this product only in commercial and farm

plantings. Do not use in greenhouses. Do not treat plants grown for transplanting. Apply within 21 days of planting or transplanting.

Use a m inimum of 10 gal water per acre for ground application

. Leafy Vegetables (non

- Brassica ) (Group 4)

Soil at Planting (in

- furrow spray, transplant water treatment, hill drench, surface band, soil shank injection) 18.66% SC

[352

- IAN]
VerimarkTM 0.176

lb ai/A

0.00202 lb ai/gal 1 0.176

lb ai/A N/A Only to be applied to the soil by ground or drip

chemigation application equipment. Must be applied uniformly in the root zone. Do not make aerial or airblast applications

. Do not treat plants being grown for transplanting in

nurseries. Use this product only in commercial and farm plantings. May be used on crops grown for seed production.

Foliar (ground, aerial) 10.20% SE

[352

- ILO]
ExirelTM 0.133

lb ai/A

0.00443 lb ai/gal N/S 0.4

lb ai/A 1 Do not treat plants grown for transplanting. Do

not apply to the soil or through drip irrigation systems. Use this product only in commercial and farm plantings. May be used on crops grown for seed production. Adjuvants may be used (methylated seed oil s; petroleum oil

concentrates: non

- ionics; organosilicones/ organosilicates). Use a minimum of 10 gallons per acre for all vegetable crops.

Soil (i n

- furrow spray at seeding or transplanting; post seeding, post transplant, hill drench; drip (trickle) chemigation;

shanked into root zone) 20.0% WG

[100

- RUER]

A16901B CP 0.175

lb ai/A

0.0175 lb ai/gal 1 0.4

lb ai/A NA Use this product only in commercial and farm

plantings. Do not use in greenhouses. Do not treat plants grown for transplanting. Apply within 21 days of planting or transplanting. Make only one soil application per growing

season.

### Page 15 of 47

Table 4.1. Summary of Proposed Directions for Use of Cyantraniliprole (DuPont and Syngenta Labels)

Application Timing, Type, and Equipment Formulation

[EPA Reg. No.]

Trade Name a Maximum

Application

Rate Max. No.

of Apps per

Season Max.

Seasonal Application

Rate RTI Use Directions and Limitations

Foliar (ground, aerial, chemigation) 20.0% WG

[100

- RUER]

A16901B CP 0.0875

lb ai/A

0.00875 lb ai/gal N/S 0.4

lb ai/A 7 Use this product only in commercial and farm

plantings. Do not use in greenhouses. Do not treat plants grown for transplanting. Apply within 21 days of planting or transplanting.

Use a m inimum of 10 gal water per acre for ground application

.

Mustard Seed

Seed treatment b 50% FS

[352

- ILI]

Dermacor®

Z

- 103 1.0

lb ai/cwt 1 0.4

lb ai/A 7 Apply as a water

- based slurry prior to planting.

May be applied with other registered seed treatment fungicides and insecticides. Use EPA

approved dye or colorant to ensure that seed pieces are dyed an unnatural color.

Oilseed Crops (Group 20) (see also rapeseed)

Foliar (ground, aerial ) 10.26% OD

[352

- ILT]
BeneviaTM 0.133

lb ai/A

0.0133 lb ai/gal N/S 0.4

lb ai/A 7 Do not treat plants grown for transplanting. Do

not apply to the soil or through drip irrigation systems. Use this product only in commercial and farm plantings. May be used on crops grown for seed production. Adjuvants may be used (methylated seed oil s; petroleum oil

concentrates: non

- ionics; organosilicones/ organosilicates). Use a minimum of 10 gallons per acre for oilseed crops.

Pome Fruits (Group 11

- 10)

Foliar (ground, aerial) 10.20% SE

[352

- ILO]
ExirelTM 0.133

lb ai/A

0.00443 lb ai/gal N/S 0.4

lb ai/A 7 Do not treat plants grown for transplanting. Do

not apply to the soil or through drip irrigation systems. Use this product only in commercial and farm plantings. May be used on crops grown for seed production. Adjuvants may be used (methylate d seed oils; petroleum oil

concentrates: non

- ionics; organosilicones/ organosilicates). Use a minimum of 30 gallons per acre for all fruit and nut crops.

Potato

Seed piece

treatment b 18.66% SC

[352

- IAN]
VerimarkTM 0.176

lb ai/A

0.010

lb ai/ cwt 1 0.176

lb ai/A N/A Apply as a water

- based slurry prior to planting.

May be applied with other registered seed treatment fungicides and insecticides. Use

EPA

- approved dye or colorant to ensure that seed pieces are dyed an unnatural color. Treat seed pieces as c lose to planting as possible. If planting is delayed, do not cover seed pieces as rotting can be accelerated. Best results are obtained if treated potatoes are allowed to dry during transit and planted the same day of

treatment. Seed piece

treatment b 48.8% FS

[100

- RUEN]

A17960A ST 0.000135 lb

ai/lb seed 1 0.000135

lb ai/lb

seed N/A

Seed piece

treatment b 48.8% FS

[100

- RURI]

A17960B ST 0.000135 lb

ai/lb seed 1 0.000135

lb ai/lb

seed N/A

Rapeseed (Canola)

Seed treatment b 50% FS

[352

- ILI]

Dermacor®

Z

- 103 1.0

lb ai/cwt 1 0.4

lb ai/A N/A Apply as a water

- based slurry prior to planting.

May be applied with other registered seed treatment fungicides and insecticides. Use EPA

approved dye or colorant to ensure that seed pieces are dyed an unnatural color.

### Page 16 of 47

Table 4.1. Summary of Proposed Directions for Use of Cyantraniliprole (DuPont and Syngenta Labels)

Application Timing, Type, and Equipment Formulation

[EPA Reg. No.]

Trade Name a Maximum

Application

Rate Max. No.

of Apps per

Season Max.

Seasonal Application

Rate RTI Use Directions and Limitations

Stone Fruits (Group 12)

Foliar (ground, aerial) 10.20% SE

[352

- ILO]
ExirelTM 0.133

lb ai/A

0.00443 lb ai/gal N/S 0.4

lb ai/A 7 Do not treat plants grown for transplanting. Do

not apply to the soil or through drip irrigation systems. Use this product only in commercial and farm plantings. May be used on crops grown for seed production. Adjuvants may be used (methylated seed oil s; petroleum oil

concentrates: non

- ionics; organosilicones/ organosilicates). Use a minimum of 30 gallons per acre for all fruit and nut crops.

Sunflower

Seed treatment b 48.8% FS

[100

- RUEN]

A17960 A ST 0.2

mg a i/ seed

0.00397

lb ai/lb seed 1 0.2 mg ai/ seed

0.00397

lb ai/lb

seed N/A Apply as a water

- based slurry prior to planting.

May be applied with other registered seed treatment fungicides and insecticides. Use EPA

approved dye or colorant to ensure that seed pieces are dyed an unnatural color. Seed treatment b 48.8% FS

[100

- RURI]

A17960 B ST 1 N/A

Tree Nuts (Group 14) and Pistachio

Foliar (ground, aerial) 10.20% SE

[352

- ILO]
ExirelTM 0.133

lb ai/A

0.00443 lb ai/gal N/S 0.4

lb ai/A 7 Do not treat plants grown for transplanting. Do

not apply to the soil or through drip irrigation systems. Use this product only in commercial and farm plantings. May be used on crops grown for seed production. Adjuvants may be used (methylated seed oil s; petroleum oil

concentrates: non

- ionics; organosilicones/ organosilicates). Use a minimum of 30 gallons per acre for all fruit and nut crops.

Foliar (ground, aerial) 10.26% OD

[352

- ILT]
BeneviaTM 0.133

lb ai/A

0.000443 lb ai/gal N/S 0.4

lb ai/A 7 Do not treat plants grown for transplanting. Do

not apply to the soil or through drip irrigation systems. Use this product only in commercial and farm plantings. May be used on crops grown for seed production. Adjuvants may be used (methylated seed oil s; petroleum oil

concentrates: non

- ionics; organosilicones/ organosilicates). Use a minimum of 30 gallons per acre for tree nuts.

Tuberous and Corm Vegetables (Subgroup 1C)

Soil at Planting (in

- furrow spray, transplant water treatment, hill drench, surface band, soil shank injection) 18.66% SC

[352

- IAN]
VerimarkTM 0.176

lb ai/A

0.010

lb ai/ cwt 1 0.176

lb ai/A N/A Only to be applied to the soil by ground or drip

chemigation application equipment. Must be applied uniformly in the root zone. Do not make aerial or airblast applications

. Do not treat plants being grown for transplanting in nurseries. Use this product only in commercial and farm plantings. May be used on crops grown for seed production.

### Page 17 of 47

Table 4.1. Summary of Proposed Directions for Use of Cyantraniliprole (DuPont and Syngenta Labels)

Application Timing, Type, and Equipment Formulation

[EPA Reg. No.]

Trade Name a Maximum

Application

Rate Max. No.

of Apps per

Season Max.

Seasonal Application

Rate RTI Use Directions and Limitations

Foliar ( ground, aerial) Chemigation (overhead only) 10.26% OD

[352

- ILT]
BeneviaTM 0.133

lb ai/A

0.0133 lb ai/gal N/S 0.4

lb ai/A 5 Do not treat plants grown for transplanting. Do

not apply to the soil or through drip irrigation systems. Use this product only in commercial and farm plantings. May be used on crops grown for seed production. Adjuvants may be used (methylated seed oil s; petroleum oil

concentrates: non

- ionics; organosilicones/ organosilicates). Use a minimum of 10 gallons per acre for tuberous and corm vegetables.

Soil (in

- furrow spray during planting; apply impregnated on dry granula r fertilizer before or during planting; at plant emergence by direct spray to

the soil near base of plant and incorporate with irrigation; at plant emergence with

overhead chemigation after hilling) 20.0% WG

[100

- RUER]

A16901B CP 0.12 5

lb ai/A

0.0125

lb ai/gal 1 0.4

lb ai/A NA Use this product only in commercial and farm

plantings. Do not use in greenhouses. Do not treat plants grown for transplanting. Apply within 21 days of planting or transplanting. Make only one soil application per growing

season

.

Residential, Commercial, Agricultural Structures (Single and multi

- family residential buildings, schools, institutional, commercial, agricultural and industrial facilities (including warehouse s, apartments, supermarkets, restaurants, motels, hotels, hospitals, daycares, and food handling/storage/processing establishments, animal production facilities, feedlots,

broiler houses, livestock barns, pet kennels) and transportation equipment such as aircraft, trains, ships, boats and buses).

Broadcast or

bait station 0.5 % G

[352

- IAE ]

HGW86 Fly Control Bait 0.0871

lb ai/A

0.00000200 lb ai/sq ft As

needed Not

specified 7 INTENDED FOR USE BY COMMERCIAL

APPLICATORS ONLY. Broadcast or scatter HGW86 fly control bait using suitable granular spreader equipment or directly from the container evenly to the target

areas. Use in indoor areas at all the above described use sites only if HGW86 fly control bait is placed in bait stations. U se commercially available bait stations that are designed to hold granular baits. When bait stations are being used, place them where the stations are inaccessible to children or pets.

Outdoor: broadcast

Indoor: c rack and crevice, including

indoor areas with exposed food/feed

present 18.66% SC

[352

- IAI]

HGW86 SC

Insect Control 0.0355

lb ai/1000 sq ft

0.00887 lb ai/gallon As

needed Not

specified 7 INTENDED FOR USE BY COMMERCIAL

APPLICATORS ONLY. Avoid spraying food and feed handling equipment. Do not apply to areas that are routinely washed such as cracks and crevices in
tops o f tables, food/feed preparation and prepared food holding surfaces. Do not apply a broadcast or general surface application to

interior surfaces of residential or commercial

structures. Do not apply this product to pets, edible crops, or sources of elect ricity. Do not make applications to structures while occupied by livestock, poultry or companion animals. Do not apply to milk rooms or feed rooms. Do not make applications to any animal f eedstuffs,

water, or watering equipment. Do not contaminate any animal food, feed, or w ater in and around livestock, poultry, or c ompanion animal housing when making applications.

### Page 18 of 47

Table 4.1. Summary of Proposed Directions for Use of Cyantraniliprole (DuPont and Syngenta Labels)

Application Timing, Type, and Equipment Formulation

[EPA Reg. No.]

Trade Name a Maximum

Application

Rate Max. No.

of Apps per

Season Max.

Seasonal Application

Rate RTI Use Directions and Limitations

Ornamentals (Ornamental plants/shrubs/trees and vegetable transplants in and around greenhouses, nurseries, interior plantscapes, lath an d shadehouses (grassy, weedy, mulched, bare soil areas in and around), trees (including non

- fruit bearing and nut trees), shrubs, evergreens, bedding plants, flowering plants, flowers, foliage plants, ground covers, vines (non

- bearing), interior plantscape p lants, vegetable transplants (including fruiting, leafy, and tuberous/corm)).

Foliar spray, soil broadcast spray, soil drench, soil injection, or chemigation 18.66% SC

[352

- IAG]

HGW86 GH&N

Insect Control 0.261

lb ai/A

0.00326 lb ai/gal 2 0.418

lb ai/A 7 Do not apply this product with aerial application

equipment. Do not apply to greenhouse or field grown vegetables, only apply to vegetable transplants grown in enclosed structures.

Foliar 18.66% SC

[352

- IAL]

HGW86 T&O

Insect Control 0.313

lb ai/A

0.00418 lb ai/gal 2 0.418

lb ai/A 7 Do not apply this product through any type of

irrigation system. Do not apply this product with aerial application equipment. Do not use on plants being grown for sale or other commercial use; or for commercial seed

pr oduction. Do not apply this product in commercial nurseries and greenhouses.

Foliar, soil, chemigation, or handheld equipment 20% WG [100

- RUEE] Mainspring

Insecticide 0.131

lb ai/A

0.00131 lb ai/gal 2 0.263

lb ai/A 14 Do not apply with aerial equipment.

Soil (individual fire ant mound treatment) 20% WG [100

- RUEE] Mainspring

Insecticide 0.00475

lb ai/gal NA NA NA For small mounds (<6 inch in diameter) apply 1 gal of water per m ound and for larger mounds apply 2

- 3 gal of dilute solution per mound for optimum control. Direct the application to the center of the mound, including a 6

- inch diameter

circle.

Foliar 20% WG

[100

- RUEG]

A16901B

Residential 0.000781

lb ai/gal 2 0.00156 lb ai/gal 7 Mix 1 teaspoon in 1 gallon of water.

Apply as a thorough cover spray. 1 gallon treats plants in a 400 square feet area.

Turfgrass (including golf courses, institutional, commercial and residential lawns, landscape, recreational, sod farms, sports fields, parks, municipal grounds and cemeteries).

Foliar 18.66% SC

[352

- IAL]

HGW86 T&O

Insect Control 0.313

lb ai/A

0.00418 lb ai/gal 2 0.418

lb ai/A 7 Do not apply this product through any type of

irrigation system. Do not apply this product with aerial application equipment. Do not use on plants being grown for sale or other commercial use; or for commercial seed production. Do not apply this product in commercial nurseries and greenhouses.

Foliar 20% WG

[100

- RUEU]

A16901B Turf

Insecticide 0.133

lb ai/A

0.00203 lb ai/gal 2 0.265

lb ai/A 30 Do not apply this product through any type of

irrigation system.

a Formulation codes: G = granular, SC = suspension concentrate, SE = suspoemulsion, WG = water dispersible granules, OD = oil dispersion, FS = flowable suspension.

b cwt = hundredweight (100 lb seed).

Seed treatment rate calculations are based on the following assumptions: Mustard seed: 90,000 to 115,000 seeds per lb (assumed to be equivalent to rapeseed/canola). Potato seed pieces: 5 to 11 seed pieces per lb. Rapeseed (canola): 90,000 to 115,000 seeds pe r lb. Sunflowers: 2,000 to 9,000 seeds per lb.

### Page 19 of 47

5 .0 Residential Exposure and Risk Estimates

At this time, t here are newly propose d residential uses of cyantraniliprole that may lead to handler and post

- application exposures for both adults and children

. Adults may be exposed during handling and post

- application activities (via dermal and inhalation routes; children may be exposed during post

- application activities (via dermal and incidental oral routes). However, since dermal hazard has not been identified for cyantraniliprole, the only exposures of concern are handler inhalation for adults, and post

- application incidental oral for children. These uses

have been assessed with current policies which includ e updates to HED’s 2012 Residential

SOPs 2 

### along with policy change s for body weight assumptions.

The end use products that may lead to residential exposures (handler and/or post

- application exposure) include the following EPs : 1. EPA Reg. No. 352

- IAE (fly ba it for use in and around residential structures);

2. EPA Reg. No. 352

- IAG (foliar and systemic insect control on ornamental plants/shrubs/trees, and interior plantscapes);

3. EPA Reg. No. 352

- IAI (for use in single and multi

- family residential buildings, schools

, apartments, and daycares); and

4. EPA Reg. No. 352

- IAL (foliar and systemic insect control in landscape and recreational turfgrass, including golf courses and interior plantscapes);

5. EPA Reg. No. 100

- RUEG (outdoor applications to residential landscape plants ); and

6. EPA Reg. No. 100

- RUEU (foliar and systemic insect control in turfgrass including golf courses, residential lawns, and recreational turfgrass).

5 .1 Residential Handler Exposure/Risk Estimates

HED uses the term “handlers” to describe those individua ls who are involved in the pesticide application process. HED believes that there are distinct tasks related to applications and that exposures can vary depending on the specifics of each task. Residential handlers are addressed somewhat differently by H ED as homeowners are assumed to complete all elements of an application without use of any protective equipment.

Of all proposed residential uses, only one WG product is intended for homeowner use: A16901B Residential (EPA Reg. No. 100

- RUEG: outdoor appl ications to residential landscape plants). However, since the other labels include residential use sites, use by homeowners is possible, and prohibition of use by homeowners is not enforceable. Thus, residential handler exposure and

risk estimates have b een calculated for all possible residential exposure scenarios. Including all possible residential exposure scenarios provides a conservative and health protective assessment for the potential for homeowners to use the professionally labeled products on r esidential use

sites. The formulations for the other labels include G and SC.

Since there are no toxicity findings for the short

- term dermal route of exposure up to the limit dose, the residential handler assessment only includes the inhalation route of exposure.

2 Available: http://www.epa.g ov/pesticides/science/residential

- exposure

- sop.html

### Page 20 of 47

Residential Handler Exposure Data and Assumptions A series of assumptions and exposure factors served as the basis for completing the residential handler risk assessments. Each assumption and factor is detailed below.

Application Rate : Refer to the proposed use pattern table in Section 4.0.

Unit Exposures and Area Treated or Amount Handled : Unit exposure values and estimates for

area treated or amount handled were taken from HED’s 2012 Residential SOPs 3 

### ( Lawns/Turf;

Gardens and Trees ; Indoor Environments )

.

Exposure Duration: Residential handler exposure is expected to be short

- term in duration.

Intermediate

- term exposures are not likely because of the intermittent nature of applications by

homeowners

.

Residential Handler Non

- Cancer Exposure and Risk Estimate Equations The algorithms used to estimate exposure and dose for residential handlers can be found in the

2012 Residential SOPs 4 

### ( Lawns/Turf; Gardens and Trees; Indoor Environments )

.

Combining Exposures/Risk Estimate s: The dermal route of exposure does not need to be combined with another route of exposure or included in the aggregate risk assessment because there is no identified dermal hazard

.

Summary of Residential Handler Non

- Cancer Exposure and Risk Estimates

Hand ler risk estimates were assessed for all possible residential handler scenarios in which homeowners may be exposed to cyantraniliprole. Risk estimates of all possible scenarios are not

of concern. Short

- term inhalation MOEs range from 22,000 to 220,000,0 00 as summarized in Table 5.1. Furthermore, these calculated risk estimates are highly conservative because the inhalation exposure POD is based on an exposure duration of 24 hours per day.

Table 5.1

. Residential Handler Non

- C ancer Exposure and Risk E stimates for Cyantraniliprole

Application Equipment Crop or Target Inhalation

Unit Exposure Maximum

Application

Rate a Amount

Handled Daily b Inhalation

Dose c MOE d

mg/lb ai mg/kg/day

Mixer/Loader/Applicator for Granular Formulations

Push

- Type Rotary Spreader Outdoor areas used for storage of

waste around commercial establishments, commercial operations, and agricultural animal production facilities 0.0026 0.0871

lb ai/A 0.5

acres 0.00000142 5

, 10 0,000

Belly Grinder 0.039

0.00000200 lb ai/sq ft 1200

sq ft 0.00000117 6,200,000

Spoon 0.087

100 sq ft 0.000000218 33,000,000 Cup 0.013 0.0000000325 220,000,000 Hand Dispersal 0.38 0.000000950 7,600,000

Shaker Can 0.013 0.0000000325 220,000,000

3 Available: http://www.epa.gov/pesticides/science/residential

- exposure

- sop.html

4 Available: http://www.epa.gov/pesticides/science/residential

- exposure

- sop.html

### Page 21 of 47

Table 5.1

. Residential Handler Non

- C ancer Exposure and Risk E stimates for Cyantraniliprole

Application Equipment Crop or Target Inhalation

Unit Exposure Maximum

Application

Rate a Amount

Handled Daily b Inhalation

Dose c MOE d

mg/lb ai mg/kg/day

Bait Station/Trap Indoor areas of residential,

institutional, public, agricultural buildings/structures, or food/feed handling establishments (including restaurants, warehouses, supermarkets, hospitals, nursing homes, motels, hotels, schools, daycares, laboratories, computer facilities, ai rcraft, buses, boats/ships, trains, pet shops and zoos) E xposure is considered negligible

.

Mixer/Loader/Applicator for Liquid Formulations

Manually

Pressurized

H andwand Indoor Spot and Crack / Crevice 1.1 0.00887 lb ai/gal 0.5

gal 0.0000610 120,000

Outdoor Broadcast: Gardens/Trees 0.018 0.00000719 lb ai/sq ft 1200

sq ft 0.00000194 3,700,000

0.00418 lb ai/gal 5

gal 0.00000470 1,500,000 Outdoor Broadcast: Lawns/Turf

Hose

- End

S prayer Outdoor Broadcast: Gardens/Trees 0.0014 0.00000719

lb ai/sq ft 1200

sq ft 0.000000151 48,000,000

0.00418 lb ai/gal 11

gal 0.000000804 9,000,000

Outdoor Broadcast: Lawns/Turf 0.022 0.313

lb ai/A 0.5

acres 0.0000431 170,000

Backpack Outdoor Broadcast: Gardens/Trees 0.14 0.00000719 lb ai/sq ft 1200

sq ft 0.0000151 480,000

0.00418 lb ai/gal 5

gal 0.0000365 200,000 Outdoor Broadcast: Lawns/Turf

Sprinkler C an Outdoor Broadcast: Gardens/Trees 0.0014 0.00000719 lb ai/sq ft 1200

sq ft 0.000000151 48,000,000

0.0014 0.00418

lb ai/gal 5

gal 0.000000365 20,000,000

Outdoor Broadcast: Lawns/Turf 0.022 0.00000719 lb ai/sq ft 1000

sq ft 0.00000198 3,600,000

Mixer/Loader/Applicator for Dry Flowable Formulations

Manually

Pressurized

H andwand Outdoor Broadcast: Gardens/Trees 1.1 0.00000301

lb ai/sq ft 1200

sq ft 0.0000497 140,000

0.00203 lb ai/gal 5

gal 0.000139 52,000 Outdoor Broadcast: Lawns/Turf

Hose

- End

S prayer Outdoor Broadcast: Gardens/Trees 0.0014 0.00000301 lb ai/sq ft 1200

sq ft 0.0000000633 110,000,000

0.00475

lb ai/gal 11

gal 0.000000914 7,900,000

Outdoor Broadcast: Lawns/Turf 0.022 0.133

lb ai/A 0.5

acres 0.0000182 400,000

### Page 22 of 47

Table 5.1

. Residential Handler Non

- C ancer Exposure and Risk E stimates for Cyantraniliprole

Application Equipment Crop or Target Inhalation

Unit Exposure Maximum

Application

Rate a Amount

Handled Daily b Inhalation

Dose c MOE d

mg/lb ai mg/kg/day

Backpack Outdoor Broadcast: Gardens/Trees

1.1 0.00000301 lb ai/sq ft 1200

sq ft 0.0000497 140,000

0.00475 lb ai/gal 5

gal 0.000327 22,000

Outdoor Broadcast: Lawns/Turf 0.00203 lb ai/gal 5

gal 0.000139 52,000

Sprinkler C an Outdoor Broadcast: Gardens/Trees 0.0014 0.00000301 lb ai/sq ft 1200

sq ft 0.0000000633 110,000,000

0.00475 lb ai/gal 5

gal 0.000000416 17,000,000

Outdoor Broadcast: Lawns/Turf 0.022 0.00000304 lb ai/sq ft 1000

sq ft 0.000000836 8

, 60 0,000

a Based on maximum application rate s on proposed labels: EPA Reg. No. 352

- IAE for granular application to indoor and outdoor areas, EPA Reg. No. 352

- IAI for liquid applications to indoor crack and crevices, EPA Reg. No. 352

- IAL for liquid applications to ornamentals and turf, EPA Reg. No. 100

- RUEE for dry flowable applications to ornamentals, and EPA Reg. No. 100

- RUEU for dry flowa ble applications to turf.

b Based on HED’s 2012 Residential SOPs: Lawns/Turf; Gardens and Trees; Indoor Environments ( http://www.epa.gov/pesticides/science/residential

- exposu re

- sop.html ).

c Inhalation Dose = Inhalation Unit Exposure (mg/lb ai) × Application Rate (lb ai/acre or lb ai/ gal) × Amount Handled ( A/day or gallons/day) ÷ BW ( 80 kg adult ).

d Inhalation MOE = Inhalation NOAEL (mg/kg/day) ÷ Inhalation Dose (mg/kg/day). Short

- Term Inhalation NOAEL = 7.2 mg/kg/day

. Level of concern = 30.



### 5

. 2 Residential Post

- A pplication Exposure/Risk Estimates

There is the potential for post

- application exposure for individuals as a result of being in an

environment that h as been previously treated with cyantraniliprole

. Since dermal hazard has not been identified for cyantraniliprole, a quantitative assessment for dermal exposure is not necessary and the only exposures of concern are for children 1 to <2 years old who may

exp erie nce incidental oral post

- application exposure to cyantraniliprole from treated turf and

indoor cracks/crevices. Furthermore, a risk assessment for incidental oral ingestion of granules has not been conducted based on a lack of hazard via the acute dietary route of exposure; and an indoor inhalation risk assessment has not been conducted because the acute inhalation toxicity is low (Toxicity Category IV), and exposure is expected to be negligible based on the low vapor

pressure of cyantraniliprole (3.85×10 - 17 

### mm Hg at 20oC) and the low proposed application rate (0.391 lb ai/A)

.

The end use products that may lead to residential post

- application exposures include the following EPs:

1. EPA Reg. No. 352

- IAE ( G fly bait for use in and around residential structures);

2. EPA Reg. No. 352

- IAI ( SC crack and crevice use in single and multi

- family residential buildings, schools , apartments, and daycares);

3. EPA Reg. No. 352

- IAL (foliar and systemic insect control in landsc ape and recreational turfgrass, including golf courses and interior plantscapes); and

### Page 23 of 47

4. EPA Reg. No. 100

- RUEU (foliar and systemic insect control in turfgrass including golf courses, residential lawns, and recreational turfgrass).

The lifestage (children 1 to <2 years old) selected for each post

- application scenario is based on an analysis provided as an Appendix in the 2012 Residential SOPs 5 

### . This lifestag e is not the only lifestage that could be potentially exposed for these post

- application scenarios; ho wever, the assessment of these lifestages is health protective for the exposures and risk estimates for any other potentially exposed lifestages.

Residential Post

- App lication Exposure Data and Assumptions A series of assumptions and exposure factors serve d as the basis for completing the residential

post

- application risk assessment . Each assumption and factor is detailed in the 2012 Residential

SOPs 5 

### (Lawns/Turf ; Indoor Environments ) and Appendix B

. Based on the SOPs, the deposited

residue value for liquid application to indoor cracks/crevices was calculated to be 1.74 μg/cm 2



### .

In addition to the SOPs, the registrant has submitted chemical

- specific turf transferrable residue (TTR) data (DP407965, N. Tsaur, 01/ 22 /2013

, Cyantraniliprole. Determination of Transferable Residues of Cyantraniliprole from Turf Treated with Water

- Dispersible Granule (WG) and Granule (GR) Formulations of Cyantraniliprole )

. The high

- end TTR value chosen to be protective of all exposure scenarios (regardless of formulation applied), is the predicted Day 0

residue from the California site of 0.0282 μg/cm 2



### . This value is based on a target application rate

of 0.20 lb ai/A and m ust be adjusted for the proposed application rates in quantitative post

application risk estimate calculations. Table 5.2.1 provides a regression summary for the TTR associated TTR study.

Table 5.2.1 . Regression Summary for Turf Treated with Two Applicat ions of C yantraniliprole a

Statistic SYN545377 WG (40) Formulation SYN545377 GR (.23)

Formulation

Pennsylvania Georgia California Georgia

Actual Average

Measured Residue on Day 0 (μg/cm 2 ) 0.031 (first application)

0.021 (second application) 0.015

(first application)

0.015 (second application) 0.027

(first application)

0.0199 (second application) 0.00063

(first application)

0.000292 (second application)

Predicted Day 0

Residue (μg/cm 2 ) 0.0158 0.0159 0.0282 b 0.000396

Slope

- 0.289

- 0.362

- 0.648

- 0.0992

Half

- life (days) 2.40 1.91 1.07 6.99

R 2 0.952 0.978 0.948 0.237 Registrant’s predicted

half

- life (days) 2.5 2.0 1.4 7.0

Registrant’s R 2 0.892 0.980 0.872 0.320

5 Available: http://www.epa.gov/pesticides/science/r esidential

- exposure

- sop.html

### Page 24 of 47

a Regression data is based on TTRs collected after the second (last) application. All applications were made at a target rate of 0.2 lb ai/A.

b The TTR value recommended for turf post

- application ri sk assessment, regardless of formulation applied.



### Residential Post

- App lication Non

- Cancer Exposure and Risk Equations The algorithms use d to estimate residential post

- application exposure and dose can be found in

th e 2012 Residential SOPs 5 

### (Lawns/Turf ; Indoor Environments ) and Appen dix B

.

Combining Exposure and Risk Estimates The dermal route of exposure does not need to be combined with the assessed incidental oral

route of exposure or included in the aggregate risk assessment because there is no identified

dermal hazard

.

Summary of Residential Post

- App lication Non

- Cancer Exposure and Risk Estimates

Table 5.2 .2 presents the post

- application incidental oral MOE values calculated from the following application scenarios:

1. liquid application of cyantraniliprole to turf

, 2. granular applicatio n to cyantraniliprole to turf, and

3. liquid application of cyantranilip r ole to indoor cracks/crevices.

Post

- application risk estimates for all scenarios are not of concern to HED (MOEs range from 290 to 1,000,000). The incidental oral sc enarios (i.e., hand

- to

- mouth and object

- to

- mouth)

should be considered inter

- related and it is likely that they occur interspersed amongst each other across time. However, combining these scenarios would be overly

- conservative because of the

conservative nature of each individual assessment. Therefore, the hand

- to

- mouth post

application exposure scenario for children 1 < 2 years old should be considered a protective estimate of children’s exposure to pesticides used indoors. Furthermore, incidental oral risk estimates are highly conservative because the short

- and intermediate

- term incidental oral POD

is based on a 90

- day exposure duration.

Table 5.2. 2

. Residential Post

- Application Non

- Cancer Exposure and Risk Estimates for Cyantraniliprole

Lifestage Post

- Application Exposure Scenario Application

Rate a Dose b MOEs c Use Site Route of Exposure mg/kg/day

Children 1 to <2 years old Liquid Application

to Turf ST Hand to Mouth 0.313

lb ai/A 0.00604 500

ST Object to Mouth 0.000184 16,000

ST/IT Incidental Soil Ingestion 0.0000106 280,000

Granular Application

to Turf ST Hand to Mouth 0.0871

lb ai/A 0.000834 3,600

ST Object to Mouth 0.0000511 59,000

ST/IT Incidental Soil Ingestion 0.00000295 1,000,000
Incidental Granular Ingestion Acute dietary hazard not identified.
Liquid Application to

Cracks/Crevices (Carpet) ST /IT Hand to Mouth

0.0000355 lb ai/sq ft 0.0103 290

ST /IT Object to Mouth 0.00137 2,200

Liquid Application to

Cracks/Crevices (Hard Surfaces) ST /IT Hand to Mouth 0.00342 880

ST /IT Object to Mouth 0.000910 3,300

a Based on registered or proposed label (Reg. No s

. 352

- IAE, 352

- IAI, 352

- IAL ). EPA Reg. No. 352

- IAE for granular application to indoor and outdoor areas,

### Page 25 of 47

EPA Reg. No. 352

- IAI for liquid applications to indoor crack and crevices, and EPA Reg. No. 352

- IAL for liquid applications to turf.

b Dose (mg/kg/day) equations:
Hand

- to

- Mouth Dose = hand residue loading ( μ g/cm 2 ) × fraction of hand mouthed (0.127) × surface area of 1 hand (150 cm 2 ) × exposure time (1.5 hrs/day) × # of replenishment intervals/hr (4 int/hr) × (1

- ((1

- saliva extraction factor (0.5))^(Number of

hand

- to

- mouth events per hour (13.9 events/hr) ÷ # of replenishment intervals/hr)) ÷ body weight (11 kg). Object

- to

- Mouth Dose = object residue loading ( μ g/cm 2 ) × un it conversion factor (0.001 mg/ μ g) × object surface area mouthed / event (10 cm 2 /event) × exposure time (1.5 hrs/day) × # replenishment intervals/hr (4 int/hr) × (1

- ((1

- saliva extraction factor (0.50))^(# Object

- to

- M outh Events/hr (8.8 events/hr) ÷ # replenishment intervals/hr)) ÷ body weight (11 kg). Soil Ingestion = soil residue (μg/g) × ingestion rate (50 mg/day) × conversion factor (0.000001 g/μg) ÷ body weight (11 kg). TTR for liquid application rate of 0.313 l b ai/A = 0.0282 μg/cm 2 × (0.313 lb ai/A ÷ 0.20 lb ai/A) = 0.0441 μg/cm 2

. TTR for granular application rate of 0.0871 lb ai/A = 0.0282 μg/cm 2 × (0.0871 lb ai/A ÷ 0.20 lb ai/A) = 0.0123 μg/cm 2

. Deposited residue for liquid application to cracks/crevices = 1.74 μg/cm 2

.

c MOE = NOAEL ÷ Daily Dose (mg/kg/day). ST/IT Incidental Oral NOAEL = 3.0 mg/kg/day. Level of concern = 100.



### 5. 3 Residential Risk Estimates for Use in Aggregate Assessment

For the purpose of the cyantraniliprole aggregate human health risk assessment, a summary of

the most protective residential exposure estimates for all proposed residential uses are provided

in Table 5.3

. Based on the residential use profile

, and the 2012 Revised Residential SOPs, only

short

- term inhalation residential ha ndler exposures (for adults) and short

- /intermediate

- term incidental oral post

- application exposures (for children) should be included in the aggregate risk

assessment. It is noted that intermediate

- term incidental oral post

- application exposures are possible (i.e. from indoor applications and form soil ingestion due to the persistence of cyantraniliprole ) ; however, the short

- term incidental oral exposures are protective of the possible

intermediate

- term i ncidental oral exposures because the POD for both durations is the same.

Although it is possible for residential handlers to have combined exposures from concurrent turf and ornamental applications (based on the proposed label for EPA Reg. No. 352

- IAL whi ch would result in an MOE of 90,000) 6 

### , the suggested exposure contribution for aggregate risk estimate is based on the most protective risk estimate from dry flowable application to ornamentals only (based on the proposed label for EPA Reg. No. 100

- RUEE wh ich results in an MOE of 22,000). The most protective risk estimate for children’s post

- application incidental oral exposures is based on indoor liquid crack/crevice application to carpets which results in an

MOE of 290.

Table 5.3

. Scenarios Recommende d for Aggregate Risk Assessment of Cyantraniliprole

Scenario Daily Dose a MOE b mg/kg/day

Adults

Residential Handler Inhalation Exposure (Applying Dry Flowables to Ornamentals with a Backpack Sprayer) 0.000327 22,0 00

Children (1 to <2 Years Old)

Post

- Application Incidental Oral Exposure : Hand

- to

- Mouth (After Liquid Application to Cracks/Crevices on Carpet) 0.0103 290

6 EPA Reg. No. 352

- IAL (SC) may lead to concurrent turf and ornamental exposures. A conservative health

protective calculation of these two exposures results in a daily dose of 0.0000431 mg/kg/day (liquid application to lawns/turf) + 0.0000365 mg/kg/day (l iquid application to gardens/trees) = 0.0000796 mg/kg/day; thus resulting in a combined MOE of 90,000 (NOAEL of 7.2 mg/kg/day ÷ 0.0000796 mg/kg/day).

### Page 26 of 47

a D aily Dose = See Table 5 .1 for a dult h andler s cenarios and Table 5 .2 .2 for post

- application incidental oral

scenarios. Adults based on EPA Reg. No. 100

- RUEE (WG). Children based on EPA Reg. No. 352

- IAI (SC).

b MOE = NOAEL/ Daily Dose (mg/kg/day)

. ST Inhalation NOAEL = 7.2 mg/kg/day. ST Inhalation LOC = 30.

ST /IT Incidental Oral = 3.0 mg/kg/day. ST Incidental Oral LOC = 100.



### 5

. 4 Spray Drift

Spray drift is always a potential source of exposure to residents nearby to spraying operations. This is particularly the case with aerial application, but, to a lesser extent, could also be a potential sou rce of exposure from the ground application method employed for cyantraniliprole

. The Agency has been working with the Spray Drift Task Force, EPA Regional Offices

, and State Lead Agencies for pesticide regulation and other parties to develop the best spr ay drift management practices (see the Agency’s Spray Drift website for more information ) 7



### . The Agency has completed its evaluation of the new database submitted by the Spray Drift Task Force, a membership of U.S. pesticide registrants, and is developing a policy on how to appropriately apply the data and the AgDRIFT computer model to its risk assessments for pesticides applied by air, orchard airblast

, and ground hydraulic methods. After the policy is in place, the Agency may impose further refinements i n spray drift management practices to reduce

off

- target drift with specific products with significant risk estimates associated with drift.

Although a quantitative residential post

- application inhalation exposure assessment was not performed as a result o f pesticide drift from neighboring treated agricultural fields, an inhalation exposure assessment was performed for flaggers. This exposure scenario is representative of a worse case inhalation (drift) exposure and may be considered protective of most out door agricultural and commercial post

- application inhalation exposure scenarios

.

It is noted that the 0.31 3 lb ai/acre application rate for turf was modeled to estimate post

application residential exposure of children. As this rate is equal to or higher than many of agricultural application rates, this scenario is protective of any incidental ingestion exposur e of

farm children vi a spray drift from agricultural cyantraniliprole applications.

5

. 5 Residential Bystander Post

- Application Inhalation Exposure

Based on the Agency's current practices, a quantitative post

- application inhalation exposure

assessment was not performed for cyantraniliprole at this time primarily because of the low acute inhalation toxicity (Toxicity Category IV), low vapor pressure ( 3.85×10 - 17 

### mm Hg at 20oC ), and the low proposed use rate (0. 391 lb ai/A). However, volatilization of pestic ides may be a source of post

- application inhalation exposure to individuals nearby pesticide applications. The Agency sought expert advice and input on issues related to volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 2010 8



### . The Agency is in the process of evaluating the SAP report and may, as appropriate, develop policies and procedures to identify the need for and, subsequently, the way to incorporate post

- application inhalation exposure into the Agency's risk assessments. If new policies or procedures are developed, the Agency may

7 Available: http://www.epa.gov/opp000 01/factsheets/spraydrift.htm

8 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html

### Page 27 of 47

revisit the need for a quantitative post

- application inh alation exposure assessment f or cyantraniliprole

.

6 .0 Occupational Exposure and Risk Estimates

6 .1 Agricultural Occupational Handler Exposure/Risk Estimates

HED uses the term handlers to describe those individuals who are involved in the pesticide application process. HED believes that there are distinct job functions or tasks related to applications and exposures can vary depending on the specifics of each t ask. Job requirements (amount of chemical used in each application), the kinds of equipment used, the target being treated, and the level of protection used by a handler can cause exposure levels to differ in a manner specific to each application event.

Based on the anticipated use patterns and current labeling, types of equipment and techniques that can potentially be used, occupational handler exposure is expected from the proposed agricultural uses. The quantitative exposure/risk assessment develope d for occupational handlers

is ba sed on several scenarios which include mixing/loading/applying various formulations of cyantraniliprole, including liquids, dry flowables, and granules. The use sites are summarized in

Section 4.0 . Methods of application include aerial, airblast, chemigation, groundboom, seed treatment, and handhel d equipment. Refer to Table 6 .1 for a detailed list of each scenario.

Occupational Handler Exposure Data and Assumptions A series of assumptions and exposure factors served as the basis for completing the occupational handler risk assessments. Each assumption and factor is detailed below on an individual basis.

Application Rate : Refer to the proposed use patter n table in Section 4.0

.

Unit Exposures: It is the policy of HED to use the best available data to assess handler exposure. Sources of generic handler data, used as surrogate data in the absence of chemical

- specific data, include PHED 1.1, the AHETF database, the Outdoor Residential Exposure Task Force (ORETF) database , or other registrant

- submitted occupational exposure studies. Some of these data are proprietary (e.g., AHETF data), and subject to the data protection provisions of FIFRA. The standard values recommended for use in predicting handler exposure that are used in this assessment, known as “unit exposures”, are outlined in the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table 9 

### ”, which, along with additional information on HED policy on use of surrogate data, including descriptions of th e various sources, can be found at the Agency website 10



### .

Area Treated or Amount Handled : The area treated or amount handled is b ased on HED Exp oSAC Policy No. 9.1. Refer to Table 6 .1 for these assumptions for each scenario.

Exposure Duration: HED class ifies exposures from 1 to 30 days as short

- term and exposures 30 days to six months as intermediate

- term. Exposure duration is determined by many things,

9 Available: http://www.epa.gov/opp00001/science/handler

- exposure

- table.pdf

10 Available: http://www.epa.gov/pesticides/science/handler

- exposure

- data.html

### Page 28 of 47

including the exposed population, the use site, the pest pressure triggering the use of the pesticide , and the cultural practices surrounding that use site. For most agricultural uses, it is reasonable to believe that occupational handlers will not apply the same chemical every day for

more than a one

- month time frame; however, there may be a large agrib usiness and/or commercial applicators who may apply a produ ct over a period of weeks (e.g. completing multiple applications for mult iple clients within a region).

Mitigation/Personal Protective Equipment: Results are presented for “baseline,” defined as a single layer of clothing consisting of a long sleeved shirt, long pants, shoes plus socks, no

protec tive gloves, and no respirator.

Occupational Handler Non

- Cancer Exposure and Risk Estimate Equations The algorithms used to estimate non

- cancer exposure and dose for occupational handlers can be found in Appendix A

.

Combining Exposures/ Risk Estimates The dermal route of exposure does not need to be combined with the assessed inhalation route of

exposure or included in the aggregate risk assessment because there is no identified dermal

hazard

.

Summary of Occupational Handler Non

- Cancer Exposure and Risk Estimates The results of the occupational handler exposure and risk assessment indicate that short

- and

in termediate

- term inhalation risks do not exceed HED’s LOC (i.e. an MOE < 3 0 for short

- term exposures and an MOE < 100 for intermediate

- term exposures ) at baseline mitigation (no PPE)

. Since the short

- and intermediate

- term PODs are the same, the inhalation MOEs are also the same, ranging from 1 ,20 0 to 3

, 9 00,000

. Note that o nly engineering control (enclosed cockpit)

data are available to assess risks to handlers operating aircrafts.

The Agency matches quantitative occupational exposure assessment with appropriate characterization of exposure potential. While HED presents quantitative risk estimates for human flaggers whe n appropriate, agricultural aviation has changed dramatically ov er the past

two decades. According the 2012 National Agricultural Aviation Association (NAAA) survey of their membership, the use of GPS for swath guidance in agricultural aviation has grown steadily from the mid 1990’s. Over the same time period, the use of human flaggers for aerial pesticide applications has decreased steadily from ~15% in the late 1990’s to only 1% in the most recent (2012) NAAA survey. The Agency will continue to monitor all available information sources to

best assess and characterize the exposure potential for human flaggers in agricultural aerial applications.

HED has no data to assess exposures to pilots using open cockpits. The only data available is for exposure to pilots in enclosed cockpits. Therefore, risks to pilots are ass essed using the engineering control (enclosed cockpits) and baseline attire (long

- sleeve shirt, long pants, shoes, and socks); per the Agency’s Worker Protection Standard stipulations for engineering controls, pilots are not required to wear protective glo ves for the duration of the application . With this level of protection, there are no risk estimates of concern for applicators.

### Page 29 of 47

Table 6 .1. Occupational Handler Non

- Cancer E xposure and Risk Estimates for Cyantraniliprole

.

Exposure Scenario Crop or Targe t a Baseline

Inhalation

Unit Exposure b Maximum

Application

Rate c Area

Treated or

Amount

Handled Daily d Baseline Inhalation

Dose e MOE f

μg/lb ai lb ai/A Acres mg/kg/day ST LOC = 30

IT LOC = 100

Mixer/Loader

Mixing/Loadi ng Dry

Flowables for Aerial Application Sod Farms

8.96 0.133 350 0.0 0520 1,900

Typical Field Crops 0.175 0.00686 1,500

Mixing/Loading Dry

Flowables for Airblast Application Nursery Plants 0.131 20 0.000 294 34 ,000

Mixing/Loading Dry

Flowables for Chemigation Application Only Typical Field Crops 0.175 350 0.00686 1,500

Greenhouse Plants
0.131 60 0.00 0883 11, 00 0 Nursery Plants

Mixing/Loading Dry

Flowables for

Groundboom Application Golf Courses

(tees and greens only) 0.133 5 0.0000743 140,000

Golf Courses (fairways, tees, and greens) 0.133 40 0.000594 17,000

Field

- Grown Ornamentals 0.131 40 0.000588 17,000
Nursery Plants 0.131 60 0.000883 11,000 Greenhouse Plants

Sod Farms 0.133 8 0 0.00119 8,500
Typical Field Crops 0.175 80 0.00156 6,500

Mixing/Loading Liquids for Aerial Application Orchard Crops

0.219 0.133 350 0.000128 79,000

Sod Farms 0.313 350 0.000300 34,000

Typical Field Crops 0.133 350 0.000128 79,000

High

- Acreage Field Crops 0.133 1200 0.000436 23,000

Mixing/Loading Liquids for Airblast Application Nursery Plants 0.261 20 0.0000143 700,000

Orchard Crops 0.133 40 0.0000145 700,000

Mixing/Loading Liquids for Chemigation Orchard Crops 0.391 350 0.000375 27,000

Sod Farms 0.313 350 0.000300 34,000

Typical Field Crops 0.133 350 0.000128 79,000

High

- Acreage Field Crops 0.133 350 0.000128 79,000

Greenhouse Plants 0.261 60 0.0000429 230,000

Nursery Plants 0.391 60 0.0000643 160,000

Mixing/Loading Liquids for

Groundboom Application Golf Courses

(tees and greens only) 0.313 5 0.00000429 2,300,000

Golf Courses (fairways, tees, and greens) 0.313 40 0.0000343 290,000

Field

- Grown Ornamentals 0.261 40 0.0000286 350,000

Nursery Plants 0.391 60 0.0000643 160,000

Greenhouse Plants 0.261 60 0.0000429 230,000

Sod Farms 0.313 80 0.0000686 150,000

Typical Field Crops 0.133 80 0.0000291 350,000

High

- Acreage Field Crops 0.133 200 0.0000728 140,000

### Page 30 of 47

Table 6 .1. Occupational Handler Non

- Cancer E xposure and Risk Estimates for Cyantraniliprole

.

Exposure Scenario Crop or Targe t a Baseline

Inhalation

Unit Exposure b Maximum

Application

Rate c Area

Treated or

Amount

Handled Daily d Baseline Inhalation

Dose e MOE f

μg/lb ai lb ai/A Acres mg/kg/day ST LOC = 30

IT LOC = 100
Applicator

Applying Sprays for Aerial Application Orchard Crops

0.068 0.133 350 0.0000395 260,000

Sod Farms 0.133 350 0.0000394 260,000 Typical Field Crops 0.175 350 0.0000521 190,000 High

- Acreage Field Crops 0.133 1200 0.000135 75,000 Applying Sprays for Airblast Application Nursery Plants 4.71 0.131 20 0.000155 65,000 Orchard Crops 0.133 40 0.000313 32,000

Applying Sprays for

Groundboom Application Golf Courses

(tees and greens only)

0.34 0.133 5 0.00000281 3,600,000

Golf Courses (fairways, tees, and greens) 0.133 40 0.0000225 450,000

Field

- Grown Ornamentals 0.131 40 0.0000224 450,000 Nursery Plants 0.131 60 0.0000335 300,000 Greenhouse Plants

Sod Farms 0.133 80 0.0000450 220,000 Typical Field Crops 0.175 80 0.0000595 170,000 High

- Acreage Field Crops 0.133 200 0.000113 89,000 Applying Granules via

Hand Dispersal Poultry/Li vestock

Houses/Horse Barns/Feedl ots 470 0.0871 1 0.000511 20,000

Flagger

Flagging for Aerial Applications Orchard Crops

0.35 0.133 350 0.00020 4 49,000

Sod Farms 0.133 350 0.000203 50,000 Typical Field Crops 0.175 350 0.000268 38,000 High

- Acreage Field Crops 0.133 350 0.000204 49,000

Mixer/Loader/Applicator

M/L/A Dry Flowables for Backpack Sprayers Greenhouse Plants (Foliar) 140 0.00131 lb ai/gal

40

gallons 0.0000919 110,000 Nursery Plants (Foliar)

Nursery Plants (Ground/Soil) 2.58 0.00475 lb ai/gal 0.00000613 1,600,000

Landscaping (trees/shrubs/bushes) 140 0.00131 lb ai/gal 0.0000919 110,000 Landscaping (plants/flowers)

Landscaping (turf, lawns, athletic fields, parks, etc) 2.58 0.00203 lb ai/gal 0.00000261 3,900,000

M/L/A Dry Flowables for Manually

Pressurized Handwand Sprayers Greenhouse Plants (Foliar)

30 0.00131 lb ai/gal 40

gallons 0.0000198 510,000 Nursery Plants (Foliar)

Landscaping (trees/shrubs/bushes)
Landscaping (plants/flowers)

Interior Landscaping
Landscaping (turf, lawns, athletic fields, parks, etc) 30 0.00203 lb ai/gal 0.0000304 330,000

### Page 31 of 47

Table 6 .1. Occupational Handler Non

- Cancer E xposure and Risk Estimates for Cyantraniliprole

.

Exposure Scenario Crop or Targe t a Baseline

Inhalation

Unit Exposure b Maximum

Application

Rate c Area

Treated or

Amount

Handled Daily d Baseline Inhalation

Dose e MOE f

μg/lb ai lb ai/A Acres mg/kg/day ST LOC = 30

IT LOC = 100

M/L/A Dry Flowables for Mechanically

Pressurized Handgun Sprayers Greenhouse Plants (Foliar)

120 0.00131

lb ai/gal

1000

gallons 0.00198 5,100

Greenhouse Plants (Ground/Soil) 0.00475 lb ai/gal 0.00713 1,400

Nursery Plants (Foliar)

3.9 0.00131 lb ai/gal 0.0000640 160,000

Nursery Plants (Ground/Soil) 0.00475 lb ai/gal 0.000231 44,000

Landscaping (trees/shrubs/bushes) 0.00131 lb ai/gal 0.0000640 160,000

Typical Field Crops (Foliar) 3.9 0.00875 lb ai/gal 0.000426 24,000

Typical Field Crops (Ground/Soil) 3.9 0.0175 lb ai/gal 0.000854 12,000

Golf Courses (tees and greens only)

42 0.133 5

acres 0.000348 29,000 Golf Courses (fairways, tees, and greens) Landscaping (turf, lawns, athletic fields, parks, etc)

M/L/A Liquids for Backpack Sprayers Orchard (Ground/Soil) 2.58 0.00443 lb ai/gal

40

gallons 0.00000571 1,800,000

Greenhouse Plants (Foliar) 140

0.00326 lb ai/gal 0.000229 44,000 Nursery Plants (Foliar)

Nursery Plants (Ground/Soil) 2.58 0.00000421 2,400,000 Landscaping (trees/shrubs/bushes) 140 0.000229 44,000 Landscaping (plants/flowers) Landscaping (turf, lawns, athletic fields, parks, etc) 2.58 0.00418 lb ai/gal 0.00000539 1,900,000

Industrial/Commercial Areas (tires, rail/junk yards, etc) 30 0.0887 lb ai/gal 0.000133 76,000 Poultry/Liv estock

Houses/Horse Barns/Feedl ots

Foundations/Perimeters 2.58 0.0000115 880,000

M/L/A Liquids for Manually

- Pressurized Handwand Sprayers Greenhouse Plants (Foliar)

30 0.00 326 lb ai/gal

40

gallons 0.0000489 2 10,000 Nursery Plants (Foliar)

Landscaping (trees/shrubs/bushes) Landscaping (plants/flowers) Landscaping (turf, lawns, athletic fields, parks, etc) 30 0.00418 lb ai/gal 0.0000626 160,000

Interior Landscaping

### Page 32 of 47

Table 6 .1. Occupational Handler Non

- Cancer E xposure and Risk Estimates for Cyantraniliprole

.

Exposure Scenario Crop or Targe t a Baseline

Inhalation

Unit Exposure b Maximum

Application

Rate c Area

Treated or

Amount

Handled Daily d Baseline Inhalation

Dose e MOE f

μg/lb ai lb ai/A Acres mg/kg/day ST LOC = 30

IT LOC = 100

Industrial/Commercial Areas (tires, rail /junk yards, etc)

30

0.00887 lb ai/gal 0.000133 76,000 Poultry/Li vestock

Houses/Horse Barns/Feedl ots

Foundations/Perimeters

Structural Areas (bridges, shipyards, home decks, foundations)

Warehouses

110 0.00448 2,100 Residential Living Spaces (homes, apartments)

Childcare

Center/Schools/Institutions

M/L/A Liquids for Mechanically

Pressurized Handgun Sprayers Orchard Crops (Foliar) 3.9 0.00443 lb ai/gal

1000

gallons 0.000216 47,000

Orchard Crops (Ground/Soil) 3.9 0.00449 lb ai/gal 0.000219 46,000

Greenhouse Plants (Foliar)

120

0.00326 lb ai/gal 0.00489 2,100 Greenhouse Plants (Ground/Soil)

Nursery Plants (Foliar)

3.9 0.000159 63,000 Nursery Plants (Ground/Soil)

Landscaping (trees/shrubs/bushes)

Industrial/Commercial Areas (tires, rail/

junk yards, etc) 3.9

0.00887 lb ai/gal 0.000433 23,000

Warehouses

79 0.00876 1,200 Poultry/Li vestock

Houses/Horse Barns/Feedl ots

Structural (bridges, shipyards, home decks, foundations, etc)

Typical Field Crops (Foliar)

3.9 0.00202 lb ai/gal 0.0000985 100,000 Typical Field Crops (Ground/Soil)

Golf Courses (tees and greens only)

1.9 0.313 5

acres 0.0000371 270,000 Golf Courses (fairways, tees, and greens)

Landscaping (turf, lawns, athletic fields, parks, etc)

### Page 33 of 47

Table 6 .1. Occupational Handler Non

- Cancer E xposure and Risk Estimates for Cyantraniliprole

.

Exposure Scenario Crop or Targe t a Baseline

Inhalation

Unit Exposure b Maximum

Application

Rate c Area

Treated or

Amount

Handled Daily d Baseline Inhalation

Dose e MOE f

μg/lb ai lb ai/A Acres mg/kg/day ST LOC = 30

IT LOC = 100

Loader/Applicator

L/A Granules for Belly

Grinders Orchard Crops

62 0.0871 1

acre 0. 0000675 150 ,000 Greenhouse Plants Nursery Plants Landscaping (trees/shrubs/bushes) Landscaping (plants/flowers) Landscaping (turf, lawns, athletic fields, parks, etc)

Industrial/Commercial Areas (tires, rail/junk yards , etc) Poultry/Li vestock

Houses/Horse Barns/Feedl ots

Foundations/Perimeters

L/A Granules for Rotary Spreaders Orchard Crops

10 0.0871 5

acres 0.0000545 18 0,000 Greenhouse Plants Nursery Plants

Golf Courses (tees and greens only)

Golf Courses (fairways, tees, and greens) Landscaping (turf, lawns, athletic fields, parks, etc)

Industrial/Commercial Areas (tires, rail/junk yards , etc)

L/A Granules for Backpack Sprayers Nursery Plants

23.8 0.0871 1

acre 0.000000313 390,000 Industrial/Commercial Areas (tires, rail/junk yards , etc)

L/A Granules for Cups Poultry/Liv estock

Houses/Horse Barns/Feedl ots 12.5 0.0871 1

acre 0.0 000136 74 0,000

L/A Granules for Spoons Poultry/Livestock

Houses/Horse Barns/Feedl ots 121 0.0871 1

acre 0.000 131 77 ,000

a “Typical Field Cro ps” include Brassica (Cole) leafy vegetables (Group 5), bulb vegetables (Group 3

- 07), bushberries (Group 13

- 07B), citrus fruits (Group 10

- 10), cotton, cucurbit vegetables (Group 9), fruiting vegetables (Group 8

- 10), leafy vegetables (non

- Brassica ) (Group 4), oilseeds (Group 2 0), pome fruits (Group 11

- 10), potatoes, stone fruits (Group 12), sunflowers, tree nuts (Group 14), tuberous and corm vegetables (Subgroup 1C)

. “High

- Acreage Field Crops” includes cotton. “Nursery Plants” include ornamentals, vegetables, trees, container s tock. “Greenhouse Plants” include ornamentals, roses, cut flowers, container stock, vegetables grown for re

- sale to consumers

. b Based on the “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table” ( March 2012 ); Level of mitigatio n = Baseline.

c Based on the maximum application rates on the proposed label s (Reg. No s

. 352

- IAE, 352

- IAG, 352

- IAI, 352

- IAL, 253

- IAN, 352

- ILA, 352

- ILI, 352

- ILO, 352

- ILT, 100

- RUEE, 100

- RUEG, 100

- RUEN, 100

- RUER, 100

- RUEU, and 100

- RURI ).

d Exposure Science Adviso ry Council Policy #9.1.

e Dermal Dose = Dermal Unit Exposure ( μ g/lb ai) × Conversion Factor (0.001 mg/ μ g) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled Daily (A or gal/day) × DAF (%) ÷ BW (kg).

f Dermal MOE = Dermal NOAEL (mg/kg/day) ÷ Dermal Dose (mg/kg/day).

g Inhalation Dose = Dermal Unit Exposure ( μ g/lb ai) × Conversion Factor (0.001 mg/ μ g) × Application Rate (lb ai/acre or gal) × Area Treated or Amount Handled Daily (A or gal/day) ÷ BW (kg).

h Inhalation MOE = Inhalat ion NOAEL (mg/kg/day) ÷ Inhalation Dose (mg/kg/day).

### Page 34 of 47

6.2 Seed Treatment Occupational Handler Exposure/Risk Estimates

HED uses the term handlers to describe those individuals who are involved in the pesticide application process. HED believes that there are distinct job functions or tasks related to applications and exposures can vary depending on the specifics of each task. Job requirements (amount of chemical used in each application), the kinds of equipment used, the target being treated, and the leve l of protection used by a handler can cause exposure levels to differ in a manner specific to each application event.

Based on the anticipated use patterns and current labeling, types of equipment and techniques that can potentially be used, occupationa l handler exposure is expected from the proposed seed

treatment uses. The quantitative exposure/risk assessment developed for occupational handlers is based on the following scenarios:

1. Mixing/loading liquids for potato seed piece treatment,

2. Planting pota to seed pieces,

3. Mixing/loading liquids for commercial seed treatment, and

4. Planting treated seed.

Occupational seed treatment handlers may experience short

- and intermediate

- term exposure to cyantraniliprole while performing seed treatment activities in commercial settings. In addition, occupational secondary handlers may experience short

- and intermediate

- term exposure while planting cyantraniliprole

- treated seeds. No chemical

- specific handler exposure data were submitted in support of this use pat tern. For assessing commercial seed treatment and seed planting activities, unit exposure data were taken from HED ExpoSAC Policy 14: SOPs for Seed

Treatment. The amount of active ingredient handled depends on the application rate (lb ai/lb seed) and the pounds of seed treated in a day (or the pounds of seed that can be planted in a day),

all of which vary depending upon the seed type. Values for the amount of seed treated and planted per day were obtained from HED ExpoSAC Policy 15.

Treating Seed (Primary Handler)

P otential occupational exposure scenarios from the use of cyantraniliprole as a commercial seed

treatment include: m ixing, loading, applying liquid formulations; b agging treated seed; s ewing bags; and m ultiple activities

. Typically

, for large

- scale commercial seed treatments, workers perform only those specific individual tasks listed above; however, it is assumed that workers also may perform multiple activities throughout the day. As a result a “multiple activities” scenario (i.e. wher e one worker performs all seed treatment tasks such as loading/applying, sewing, bagging, cleaning, calibration, repair, forklift driver, etc.) w as addressed.

Planting Treated Seed (Secondary Handler)

P otential occupational exposure scenarios from the use of cyantraniliprole as a commercial seed

treatment include p lanting treated seed (secondary handler)

. Planting treated seed consists of the farmer purchasing bags of treated seed, placing the seed in t he hoppe r and applying seed to fields ( considered a secondary handler exposure scenario )

.

### Page 35 of 47

Potato Seed Piece Treatment HED considers commercial seed piece treatment to be either at a seed treatment facility or on

farm treatment that utilizes similar equi pment. Potato seed piece handling and seed treatment in operations large enough to facilitate commercial farm scale planting all utilize equipment that is similar in principle and in treatment capability. There are two basic types of machines. In one, seed pieces are treated (sprayed) as they move on a conveyer belt through a covered (shielded/hooded) machine that applies the spray. The other types of machines are “drums” (similar in concept to a concrete mixer) in which the seed pieces are treated as they pass through. These types of machines make it possible to treat the large volumes of seed necessary to facilitate planting on field scale operations. Most operations intend to treat only enough seed that may be planted on a given day.

Large scale ( commercial) potato seed piece treatment typically involves the following procedures. Seed potatoes are handled with some type of front end loader to dump them into a machine that cuts them into “seed pieces”. The pieces emerge on a conveyer where an

ind ividual(s) sorts and culls the pieces. Pieces too large are cut again by hand and diseased or damaged pieces are culled. The seed pieces proceed by conveyer through the spray treatment machine as described above. There is no applicator in a typical sens e of an individual using any type of sprayer to apply the material. It is applied in an automated fashion in a covered device. Finally, treated seed is again mechanically loaded in bulk to potato seed planters. Planters are similar in concept to other t ypes of machines that plant seeds. Potato planters are basically large open bins filled with seed pieces. The pieces pass through complicated “handling” machinery in the planter to very precisely deposit properly spaced seed to an optimum depth in a furr ow and are covered as the planter moves down the row.

Thus, the only occupational pesticide “handler” is the individual who prepares the stock spray solution that is used in the enclosed spray applicators. As such, that individual performs

activities whi ch are essentially the same as those performed by a mixer/loader supporting conventional ground or aerial spray operations.

Occupational Handler Exposure Data and Assumptions A series of assumptions and exposure factors served as the basis for completing the occupational handler risk assessments. Each assumption and factor is detailed below on an individual basis.

Application Rate : Refer to the proposed use pattern table in Section 4.0.

Unit Exposures: It is the policy of HED to use the best availabl e data to assess handler exposure.

Chemical

- specific data for assessing exposure during commercial seed treatment and seed planting were not submitted to the Agency in support of this Section 3 application. U nit exposures are from ExpoSAC Policy 14: SOPs for Seed Treatment ( May 1, 2003 ) and are based on data for open mixing/ loading/application systems ; and D378750 (Potato seed piece handler unit exposures).

Amount Handled : HED is currently in the process of revising ExpoSAC Policy 15: Amount of Seed Treated or Planted per Day ( March 2, 2004 ) in efforts to update the daily amount of seed treated in

### Page 36 of 47

commercial seed treatment facilities. With the increasing demand for hybridized treated seeds, there have been modifications not only in the seed treatment equipment, but in the market shares of new and currently registered pesticide products. HED understands that d ue to the high cost of producing hybrid seeds, direct seeding is done in a precision manner which requires lower volumes of seed per acre. Howe ver, this does not provide a direct correlation to the amount of

seed which is treated in the commercial seed treatment facilities.

The amount of seed handled (for both primary/treater and secondary/planter handlers) is based

on HED ExpoSAC Poli cy 15, HED ExpoSAC Policy SOP 15 .1

, and the BEAD memo : “ Acres Planted Per Day and Seeding Rates of Crops Grown in the United States. ” Note: It was assumed that the amount of potato seed pieces planted per day is equal to the amount treated per day

because it is not recommended to store potato seed pieces more than a few days after treatment.

The amount of seed treated per day at a commercial facility for short

- term exposure duration i s summarized below for each crop

. Potato Seed Pieces

– 800,0 00 lbs, Rapeseed/Canola

– 125 ,000 lbs,

Mustard Seed

– 125 ,000 lbs, and

Sunflowers

– 339,5 00 lbs

.

T he amount of seed planted per day i s summarized below for each crop

. Potato Seed Pieces

– 800,000 lbs, Rapeseed/Canola

– 400 lbs,

Mustard Seed

– 560 lbs, and

Sunfl owers

– 32 0 lbs

.

Exposure Duration: HED classifies exposures from 1 to 30 days as short

- term and exposures 30 days to si x months

as intermediate

- term.

Mitigation/Personal Protective Equipment: Resu lts are presented for “baseline ” ( defined as a single layer of clothing consisting of a long sleeved shirt, long pants, shoes plus socks, no protective gloves, and no respirator.

Occupational Handler Non

- Cancer Exposure and Risk Estimate Equations The algorithms used to estimate non

- cance r exposure and dose for occupational handlers can be found in Appendix A.

Combining Exposures/Risk Estimates The dermal route of exposure does not need to be combined with the assessed inhalation route of

exposure or included in the aggregate risk assessment because there is no identified dermal

hazard

.

Summary of Occupational Handler Non

- Cancer Exposure and Risk Estimates The results of the occupational handler exposure and risk asse ssment indicate that short

- term inhalation risks do not exceed HED’s LOC (i.e. an MOE < 3 0 for short

- term exposures ) at

### Page 37 of 47

baseline mitigation (no PPE). Short

- term exposure risk estimates are protective of intermediate

term exposure risk estimates because the throughput (amount of se ed treated) is greater than, or equal to, the throughput of short

- term exposure. The calculated inhalation risk estimates do not
exceed HED’s LOC for intermediate

- term exposures (i.e. an MOE < 100 ) at baseline mitigation (no PPE)

. T he inhalation MOE s ran ge from 370 to 190,000 for handlers ( treaters and planters).

Table 6.2

. Summary of Short

- Term Handler Exposures and Risks for Cyantraniliprole a

Seed Type Max

App lication

Rate b Inhal ation

UE c Am oun t of Seed

Treated or Planted Per Day d Inhal ation

Dose e Inhal ation

MOE f

lb ai/lb seed mg/lb lb seed/day mg/kg/day ST LOC = 3 0

Loader/Applicator

Potato Seed Pieces 0.000135 0.0064 * 800,000 0.00864002 1,200 Rapeseed/Canola 0.0100

0.00034 125,000 0.00531939 1,900

Mustard Seed 0.0100 125,000 0.00531939 1,900

Sunflowers 0.00397 339,500 0.00572580 1,800

Sewer
Rapeseed/Canola 0.0100

0.00023 125,000 0.00359841 2,800

Mustard Seed 0.0100 125,000 0.00359841 2,800

Sunflowers 0.00397 339,500 0.00387333 2,600 Bagger Rapeseed/Canola 0.0100

0.00016 125,000 0.00250324 4,000

Mustard Seed 0.0100 125,000 0.00250324 4,000

Sunflowers 0.00397 339,500 0.00269449 3,700

Multiple Activities

Rapeseed/Canola 0.0100

0.0016 125,000 0.02503242 400

Mustard Seed 0.0100 125,000 0.02503242 400

Sunflowers 0.00397 339,500 0.02694492 370

Planter

Potato Seed Pieces 0.000135

0.0034 800,000 0.0045900 2,200
Rapeseed/Canola 0.0100 400 0.0001702 59,000

Mustard Seed 0.0100 560 0.0002383 42,000

Sunflowers 0.00397 320 0.0000540 190,000

a Seed treatment rate calculations are based on the following assumptions: Mustard seed: 90,000 to 115,000 seeds per lb; 7 lbs of seed planted per day, 80 acres planted per day. Potato seed pieces: 5 to 11 seed pieces per lb; 800,000 seed pieces planted per day. Rapeseed (ca nola): 90,000 to 115,000 seeds per lb; 5 lbs of seed planted per day, 80 acres planted per day. Sunflowers: 2,000 to 9,000 seeds per lb; 4 lbs of seed planted per day, 80 acres planted per day.

b Application Rates based on proposed label uses for cyantraniliprole (EPA Reg. Nos. 352

- IAN, 100

- RUEN, and 100

- RURI).

c Unit Exposures from HED Exposure Science Advisory Council Policy 14 : Standard Operating Procedures for Seed Treatment (baseline inhalation = no respirator). * The inhalation unit exposure for potato seed pieces comes from D378750

. d HED default for lb seed treated/ planted per day from HED Exposure Science Advisory Council Interim Policy 15 .1 and the BEAD memo

“ Acres Planted Per Day and Seeding Rates of Crops G rown in the United States ” ( J. Becker, March 2011).

e Daily Inhalation Dose (mg/kg/day) = daily inhalation unit exposure ( m g/ lb ai) × a pplication rate (lb ai/lb seed) × amount planted (lb seed/day)

÷ body weight (8 0 kg adult).

f Inhalation MOE = NOAEL ( 10 .0 8 mg/kg/day for short

- and intermediate

- term exposure ) ÷ Inhalation Dose (mg/kg/day)

. Short

- term level of

concern = 3 0.

### Page 38 of 47

On

- Farm Seed Treatment

On

- farm seed treatment utilizes similar machinery as commercial seed treatment; the only difference being the size of the equipment. T he assessed commercial seed treatment exposure and risk is protective of on

- farm seed treatment scenarios.

6

. 3 Occupational Post

- App lication Exposure/ Risk Estimates

HED uses the term post

- application to describe exposures that occur when individuals are present in an environment that has been previously treated with a pesticide (also referred to as re

entry exposure). Such exposures may occur when workers enter previously treated areas to perform job functions, including activities related to crop production, such as scouting for pests or harvesting. Post

- app lication exposure levels vary over time and depend o n such things as the type of activity, the nature of the crop or target that was treated, the type of pesticide application, and the chemical’s degradation properties. In addition, the timing of pesticide applications, relative to harvest activities, can greatly reduce the potential for post

- application exposure.

An occupational post

- application dermal exposure and risk assessment was not conducted because a dermal hazard was not identified for cyantraniliprole.

With regard to seed treatment, the potential for post

- application exposures following the planting

of cyantraniliprole

- treated seeds is unlikely because s ustained levels of contact with treated seed after it has been placed in the soil or other planting media would not be expected because no routine cultural practice required for the production of agricult ural commodities involves such an activity as defined in the no/low contact criteria in the Worker Protection Standard (WPS)

. Therefore, no quantitative post

- application assessment is required for exposure to treated seeds that have already been planted

.

Occupational Post

- Application Inhalation Exposure/Risk Estimates Based on the Agency's current practices, a quantitative post

- application inhalation exposure

a ssessment was not performed for cyantraniliprole at this time primarily because of the low acute inhalation toxicity (Toxicity Category IV), low vapor pressure ( 3.85×10 - 17 

### mm Hg at 20oC ), and the low proposed use rate (0. 391 lb ai/A). However, there are multiple potential sources of post

application inhalation exposure to individuals performing post

- application activities in previously treated fields. These potential sources include volatilization of pesticides and resuspension of dusts and/or particulates that contain pesticides. The Agency sought expert advice and input on issues related to volat ilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on March 2, 2010 11



### . The Agency is in the process of evaluating the SAP report as well as available post

- application inhalation exposure data generated by the

ARTF and may, as appropriate, develop policies and procedures, to identify the need for and, subsequently, the way to incorporate occupational post

- application inhalation exposure into the Agency's risk assessments. If new policies or procedures are put into place, the Agency may revisit the need for a quantitative occupational post

- application inh alation exposure assessment for cyantraniliprole

.

11 Available: http://www.epa.gov/scipoly/SAP/meetings/2009/120109meeting.html

### Page 39 of 47

Although a quantitative occupational p ost

- application inhalation exposure assessment was not performed, an inhalation exposure assessment was performed for occupational/commercial handlers. Handler exposure resulting from application of pesticides outdoors is likely to result in higher exposu re than post

- application exposure. Therefore, it is expected that these handler inhalation exposure estimates would be protective of most occupational post

- application inhalation exposure scenarios.

Greenhouse Uses The Worker Protection Standard for Agri cultural Pesticides contains requirements for protecting workers from inhalation exposures during and after greenhouse applications through the use of ventilation requirements. 12



### Indoor Commercial Uses Commercial applicators do not typically return to the treated areas after an indoor commercial pesticide application (sites such as warehouses, food handling establishments, and hotels, etc.) and thus an occupational post

- application inhalation exposure assessment was not performed for commercial applicators.

Seed Treatment Uses

A post

- application inhalation exposure assessment is not required as exposure is expected to be negligible. Seed treatment assessments provide quantitative inhalation exposure assessments for seed treaters and secondary handlers (i.e. planters). It is expected that these exposure estimates would be protective of most post

- application inhalation exposure scenarios.

6.4 Restricted Entry Interval

Cyantraniliprole is classified as Toxicity Category IV via the dermal route. It is not irritating to

the skin and it is not a sk in sensitizer. Typically, the REI specified on the proposed label is based on the acute toxicity of the active ingredient. Under 40 CFR 156.208 (c) (2) (iii), active ingredients classified as Acute III or IV for acute dermal, eye irritation and primary s kin irrigation are assigned a 12

- hour REI. However , REIs may be further reduced from 12 hours if

certain criteria are met for both the technical material and the different end

- use products in

accordance with the Pesticide Registration (PR) Notice 95

- 3 [Re d uction of Worker P rotection Standard (WPS) Interim Restricted Entry Intervals (REIs) for Certain Low Risk Pesticides]. 13



### The criteria for reducing REIs include the following: (1) The active ingredient is in Toxicity Category III or IV based upon data for acute dermal toxicity, acute inhalation toxicity, primary skin irritation, and primary eye irritation. (2) The active ingredient is not a dermal sensitizer. (3) The active ingredient is not a cholinesterase inhibitor. (4) The active ingredient is not associated with k nown reproductive, developmental, carcinogenic, or neurotoxic effects. (5) EPA does not possess incident information that are “definitely” or “probably” related to the post

- application exposures to the active ingredient.

12 40 CFR 170.110, (3) (Restrictions associat ed with pesticide applications)

13 Available: http://www.epa.gov/PR_Notices/pr95

- 3.html

### Page 40 of 47

With respect to the active ingredient, cyantraniliprole, these criteria have been met for the technical and all but two of the proposed EPs. Since the two products, EPA Reg. No. 352

- ILT and EPA Reg. No. 352

- ILI, have been identified as dermal sensitizers, a 12

- hour REI is required

to protect agricultural workers from post

- application exposures to cyantraniliprole. Aside from these two products, a 4

- hour REI is adequate . Table 6.4 shows the acute toxicity results for each proposed label and formulation.

Table 6.4

. Acute Toxicity Results of All Proposed U.S. Registrations for Cyantraniliprole

EPA Reg . No. Formulation Oral Dermal Inhalation Skin Irrit ation Eye Irrit ation Sens itization

352

- ILA 96.7% technical IV IV IV IV IV

- ve

352

- ILT 100 g/l OD IV IV IV IV III +ve

352

- ILO 100 g/l SE IV IV IV III III +ve

352

- IAN 200 g/l SC IV IV IV IV IV

- ve

352

- ILI 625 g/l FS IV IV IV IV IV

- ve

352

- IAE 0.5% RB IV IV w aived a IV IV

- ve

352

- IAI 200 g/l SC IV IV IV IV IV

- ve

352

- IAL 200 g/l SC IV IV IV IV IV

- ve

352

- IAG 200 g/l SC IV IV IV IV IV

- ve

100

- RUER 200 +200 g/kg WG IV IV IV IV III

- ve

100

- RUEE 200 +200 g/kg WG IV IV IV IV III

- ve

100

- RUEG 200 +200 g/kg WG IV IV IV IV III

- ve

100

- RUEU 200 +200 g/kg WG IV IV IV IV III

- ve

100

- RUEN 600 g/l FS IV IV IV IV IV

- ve

100

- RURI 600 g/l FS IV IV IV IV III

- ve

a Waiver request granted (Technical = Tox Cat IV; Bait station, no potential for inhalation exposure, etc.)

### Page 41 of 47

Appendix A. Summary of Occupational Handler Non

- Cancer Algorithms

Average Daily Dose Potential daily exposures for occupational handlers are calculated using the following formulas:

where:

E = e xposure (mg ai/day),

UE = u nit e xposure (μg ai/lb ai),

AR = m aximum application rate according to proposed label (lb ai A or lb ai/gal), and

A = a rea treated or amount handled (e.g., A/day, gal/day).

The daily doses are calculated using the following formula:

where:

ADD = average daily dose absorbed in a given scenario (mg ai/kg/day),

E = e xposure (mg ai/day),

AF = absorption fa ctor (dermal and/or inhalation), and

BW = body weight (kg).

Margin of Exposure

Non

- cancer risk estimates for each application handler scenario are calculated using a Margin of Exposure (MOE), which is a ratio of the toxicological endpoint to the daily dose of concern. The daily dermal and inhalation dose received by occupational handlers a re compared to the appropriate POD ( i.e.

, NOAEL) to assess the risk to occupational handlers for each exposure

route. All MOE values a re calculated using the following formula:

where:

MOE = margin of exposure: value used by HED to represent risk estimates (unitless),

POD = point of departure (mg/kg/day), and

ADD = average daily dose absorbed in a given scenario (mg ai/kg/day).

### Page 42 of 47

Appendix B . Summary of Residential Post

- Ap plication Non

- Cancer Algorithms

Dose, normalized to body weight, is calculated as:

where:

D = dose ( mg/kg/day );

E = exposure (mg/day); and

BW = body weight (kg).

Post

- A pplication Hand

- to

- Mouth Exposure Algorithm for Physical Activities on Turf Exposure from hand

- to

- mouth activity is calculated as follows (based on the algorithm utilized in

the SHEDS

- Multimedia model ):

E = [HR * ( F

M 

### * SA H 

### ) * (ET * N_Replen) * (1

- (1

- SE ) (Freq_HtM/N

- Replen) 

### )]

where: E = exposure (mg/day); HR = hand residue loading (mg/cm 2 

### ); FM = fraction hand surface area mouthed / event (fraction/event); SAH = typical surface area of one hand (cm 2 

### ); ET = exposure time (hr/day); N_Replen = number of replenishment intervals per hour (intervals/hour ); SE = saliva extraction factor (i.e., mouthing removal efficiency); and Freq_HtM = number of hand

- to

- mouth contacts events per hour (events/hour).

and

where: HR = hand residue loading (mg/cm 2 

### );

Fai hands 

### = fraction ai on hands co mpared to total surface residue from dermal transfer coefficient study (unitless); DE = dermal exposure (mg); and

SA H 

### = typical surface area of one hand (cm 2 

### ).

Post

- A pplication Object

- to

- Mouth Exposure Algorithm for Physical Activities on Turf Exposure from object

- to

- mouth activity is calculated as follows (based on the algorithm utilized

in SHEDS

- Multimedia): E = [OR* CF1 * SAM O 

### * (ET * N_Replen) * (1

- (1

- SE O 

### ) (Freq_OtM/N_Replen) 

### )]

where: E = exposure (mg/day); OR = chemical residue loading on the object on day “t” (ug/cm 2 

### ); CF1 = weight unit conversion factor (0.001 mg/μg);

SAM O 

### = area of the object surface that is mouthed (cm 2 

### /event); ET = exposure time (hr/day); N_Replen = number of replenishment intervals per hour (intervals/hour);

SE O 

### = saliva extraction factor (i.e., mouthing removal efficiency); and

### Page 43 of 47

Freq_OtM = number of object

- to

- mouth contact events per hour (events/hour).

and

OR = AR * F O 

### * CF2 * CF3

where: OR = chemical residue loading on the object (μg/cm 2 

### ); AR = application rate (lbs ai/ft 2 

### or lb ai/acre);

F O 

### = fraction of residue available on the object (unitless); CF2 = weight unit conversion factor (4.54 x 10 8 

### μg/lb); and CF3 = area unit conversion factor (1.08 x 10 - 3 

### ft 2 

### /cm 2 

### or 2.47 x 10 - 8 

### acre/cm 2 

### ).

Post

- A pplication Incidental So il Ingestion Exposure Algorithm for Physical Activities on Turf Exposure from incidental soil ingestion is calculated as follows: E = SRt * SIgR * CF1

where: E = exposure (mg/day); SRt = soil residue on day "t" (μg/g); SIgR = ingestion rate of soil (mg/d ay); and CF1 = weight unit conversion factor (1 x 10 - 6 

### g/μg).

and SRt = AR * FS * (1

- F D 

### ) t 

### * CF2 * CF3 * CF4

where:

SR t 

### = soil residue on day "t" (μg/g); AR = application rate (lbs ai/ft 2 

### or lb ai/acre); FS = fraction of ai available in uppermost cm of soil (fraction/cm);

F D 

### = fraction of residue that dissipates daily (unitless); T = post

- application day on which exposure is being assessed; CF2 = weight unit conversion factor (4.54 x 10 8 

### μg/lb); CF3 = area unit conversion factor (1.08 x 10 - 3 

### ft 2 

### /cm 2 

### or 2 .47 x 10 - 8 

### acre/cm 2 

### ); and CF4 = soil volume to weight unit conversion factor (0.67 cm 3 

### /g soil).

Post

- A pplication Hand

- to

- Mouth Exposure Algorithm for Indoor Environments Exposure from hand

- to

- mouth activity is calculated as follows (based on algorithm uti lized in

SHEDS

- Multimedia):

where:

E = exposure (mg/day);

HR = hand residue loading (mg/cm 2 

### );

F M 

### = fraction hand surface area mouthed / event (fraction/event);

ET = exposure time (hr/day);

SA H 

### = surface area of one hand (cm 2 

### ); N_Replen = number of replenishment intervals per hour (intervals/hour);

SE = saliva extraction factor (i.e., mouthing removal efficiency); and Freq_HtM = number of hand

- to

- mouth contacts events per hour (events/hour).

and

### Page 44 of 47

where :
HR = hand residue loading (mg/cm 2 

### );

Fai hands 

### = fraction ai on hands compared to total surface residue from jazzercise study (unitless);

DE = dermal exposure (mg); and

SA H 

### = typical surface area of one hand (cm 2 

### ).

Post

- A pplication Object

- to

- Mouth Exposure Algorithm for Indoor Environments Exposure from object

- to

- mouth activity is calculated as follows (based on algorithm utilized in

SHEDS

- Multimedia):

where:

E = exposure (mg/day);

OR = chemical residue loading on an object ( g/cm 2 

### );

CF1 = weight unit conversion factor (0.001 mg/ g);

SAM O 

### = area of the object surface that is mouthed (cm 2 

### /event);

ET = exposure time (hr/day); N_Replen = number of replenishment intervals per hour (intervals/hour);

SE = saliva extraction factor (i.e., mouthing removal efficiency); and Freq_OtM = number of object

- to

- mouth contact events per hour (events/hour).

and

where : OR = chemical residue loading on the object (μg/cm 2 

### ); DepR = deposited residue (μg/cm 2 

### ); and

F O 

### = fraction of residue transferred to an object (unitless).

### Page 45 of 47

Appendix C

. H uman Equivalent Concentrations and Human Equivalent Dose

Calculations

The HEC and human equivalent dose calculations were based on the results of a 28

- day rat inhalation study in rats (MRID 48 697401 ) . In this study, cyantraniliprole was administered (as an aerosol) to Crl:CD(SD) rats (10/sex/dose) for 6 hours/ day, 5 days/week, for 4

- weeks. The test animals were exposed nose

- only to target concentrations of 0 (air control), 1, 10, or 100 mg/m3 of cyantraniliprole (equivalent to 0.001, 0.01, and 0.1 mg/L, respectively). Adverse effects were

not seen at any conc entration tested, although laryngeal metaplasia was considered treatment

related but not adverse at 0.1 mg/L. The NOAEL was 0.1 mg/L.

RDDR for Cyantraniliprole Calculations used to estimate the inhalation risk to humans from aerosols are dependent not on the regional gas dose ratio (RGDR) as for gases, but on the regional deposited dose ratio (RDDR). Inhalation studies using aerosols characterize particulate exposure by defining the particulate diameter [mass median aerodynamic diameter (MMAD)] and the g eometric standard deviation (σ g 

### ), which is then used to determine the RDDR. The RDDR is a multiplicative factor used to adjust an observed inhalation particulate exposure concentration of an animal (A) to the predicted inhalation particulate exposure conc entration for a human (H) that would be associated with the same dose delivered to the affected region (r) or target tissue.

RDDR

r 

### = (RDD

r



### /Normalizing Factor) A / 

### (RDD

r 

### /Normalizing Factor) H



### As with calculations for gases, the affected regions and potential target tissues are the three respiratory regions (extrathoracic, tracheobronchial, and pulmonary). The RDDR is easily calculated by using a software program designed specifically for computing the RDDR from the

MMAD and σ g 

### defined from an aeroso l inhalation study. The values for the species

- specific parameters used to calculate the RDDR are provided in the EPA document “Methods for Derivation of Inhalation Reference Concentrations and Application of Inhalation Dosimetry.” The magnitude of the U Fs applied is dependent on the methodology used to calculate risk. The RfC methodology takes into consideration the PK differences, but not the PD differences

. Consequently, the UF for interspecies extrapolation may be reduced to 3X (to account for the P D differences) while the UF for intraspecies variation is retained at 10X. Thus, the UF when using the RfC methodology is customarily 30X.

Regional Deposited Dose Ratio (RDDR)

MMAD = 3

. 00 Sigma g = 2. 30

SPECIES Body Weight (g) Minute Ventilation (VE, ml) deposited fraction

rat 236 1 71

. 5 0.587

human 70000 13800.0 0.759

RATIO 0.7 34

RDDR = (VE/ SA ) animal 

### ÷ (VE/ SA ) human 

### × deposited fraction animal 

### ÷ d eposited fraction human 

### = ( 171.5 / 236 ) animal 

### ÷ (13800/ 700 00 ) human 

### × 0. 587 ÷ 0. 759

= 2.8

### Page 46 of 47

Example for HEC calculations for short

- term occupational exposure: Assume workers will be in the greenhouse for 8 hrs/day and 5 days/week:

HEC = NOAEL study × (daily duration of exposure animal ÷ daily duration of exposure human ) × (days/week of

exposure animal ÷ days/week of exposure human ) × RDDR



### HEC = 0.1 mg/ L × (6 ÷ 8) × (5 ÷ 5) × 2.8 = 0.21 mg/L

Table B.4. HEC Array for Non

- Occupational and Occupational Risk Assessment

Relevant Study LOAEL (mg/L) NOAEL

(mg/L) Da Dh Wa Wh RDDR HEC (mg/L) inter intra UF

Short

- & Intermediate

- Term Occupational Exposure

Inhalation

– Rat (MRID 48697401 ) 28

- day Not Obs. 0.1 6 8 5 5 2.8 0.21 3 10 NA

Short

- & Intermediate

- Term Non

- Occupational (Residential) Exposure

Inhalation

– Rat (MRID 48697401 ) 28

- day Not Obs. 0.1 6 24 5 7 2.8 0.05 3 10 NA

Long Term Exposure: Not A ppropriate

Key:

LOAEL : Lowest observed adverse effect level

Da : Daily animal exposure (hrs/day)

Wa : Weekly animal exposure (days/week)

RRDR : Regional Deposited Dose Ratio

inter : interspecies extrapolation uncertainty factor Dh : Anticipated daily human exposure (hrs/day)

Wh : Anticipated weekly human exposure (days/week)

HC: Human Concentration

HEC : Human Equivalent Concentration

intra : intrasp ecies variation uncertainty factor

UF : Other uncertainty factor(s)



### Summary of Human Equivalent Concentrations
Occupational Short

- Term

Study NOAEL ( m/L)

systemic RDDR Daily Duration

( 6 hrs rat/8 hrs human) Weekly (days/week)

Duration (rat 5 days/human 5 days) HEC (mg/L) UF

28

- day rat 0.1 2.8 0.75 1 0.21 30

Non

- Occupational Short

- Term

Study NOAEL (m/L)

systemic RDDR Daily Duration

(6 hrs rat/24 hrs human) Weekly (days/week)

Duration (rat 5 days/human 7 days) HEC (mg/L) UF

28

- day rat 0.1 2.8 0.25 0.714 0.05 30



### Human Equivalent Doses The HEC is in mg/L but exposure data are in mg/kg/day. Therefore, conversion of the human mg/L value to human mg/kg/day was conducted as follows:

Inhalation to Oral Equation: dose (systemic HEC value) mg/L × A × CF (L/hr/kg) × D (hours) × AF = mg/kg;

### Page 47 of 47

Occupational: (0.21 mg/L) × 1 × 6 × 8 × 1 = 10.08 mg/kg/day

Residential : (0.05 mg/L) × 1 × 6 × 24 × 1 = 7.2 mg /kg/day

Where:

A absorption: ratio of deposition and absorption in respiratory tract compared to abs orption by the oral route. A

default A of 1 was used.

CF Conversion Factor: A L/hr/kg factor which accounts for respiratory volume and body weight for a given species and strain ( A human conversion factor of 6 for ages 10

- 30 yrs was used for both occupati onal and non

occupational calculations ).

D Duration: Duration of daily animal or human exposure (hours). The default assumption for occupational is 8

hrs while non

- occupational could potentially be 24 hrs.

AF Activity Factor: The default human activity f actor is 1.